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Yang XE, Zhang SJ, Liu Y, Yao SY, Zhang SX, Liu XM, Liang LX, Wang F. Amoxicillin high-dose dual therapy for Helicobacter pylori primary eradication: Proton pump inhibitor and potassium-competitive acid blocker, which's better? World J Gastroenterol 2025; 31:100863. [PMID: 40248055 PMCID: PMC12001176 DOI: 10.3748/wjg.v31.i13.100863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 02/22/2025] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori (H. pylori). AIM To assess the efficacy and safety of high-dose dual therapy (HDDT) utilizing various highly potent antisecretory medications, thereby providing additional clinical guidance for H. pylori eradication. METHODS The study population comprised untreated H. pylori patients from three medical centers in central China. From February 10, 2024 to March 31, 2024, 439 subjects were randomly allocated to either the esomeprazole-amoxicillin (EA) or esomeprazole-amoxicillin-clarithromycin-bismuth (B-quadruple) group. Subsequently, from April 1, 2024 to May 10, 2024, 367 subjects were randomly assigned to either the vonoprazan-amoxicillin (VA) or vonoprazan-amoxicillin-clarithromycin (VAC) group. The study recorded treatment efficacy, adverse events, compliance, symptom alleviation, and associated costs. RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat (mITT) and per-protocol (PP) analyses (P < 0.025). However, the eradication rate of EA was lower than that of the B-quadruple group [70.59% vs 83.49%, 92.86% vs 98.38%, 93.94% vs 98.38%, intention-to-treat (ITT), mITT, PP respectively, P < 0.05]. In ITT, mITT, and PP analyses, VA-dual was non-inferior to VAC treatment (84.15% vs 83.15%, 96.25% vs 92.73%, 96.75% vs 93.75%, P < 0.025). No significant differences were observed in adverse events, compliance, and symptom relief between groups. VA exhibited the lowest cost. Antibiotic use within 2 years, poor compliance, and suburban residence were associated with reduced eradication efficacy (P < 0.05). CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen, suggesting its potential as a recommended first-line treatment for H. pylori eradication. While B-quadruple therapy showed better eradication rate than EA therapy, the latter proved non-inferior in mITT and PP analyses. Notably, antibiotic use within the preceding two years, adherence to treatment protocols, and patient residence emerged as critical factors influencing eradication success.
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Affiliation(s)
- Xue-Er Yang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Sheng-Jun Zhang
- Department of Gastroenterology, The Second People's Hospital of Huaihua, Huaihua 418000, Hunan Province, China
| | - Yuan Liu
- Department of Gastroenterology, Yueyang Hospital of Traditional Chinese Medicine, Yueyang 414100, Hunan Province, China
| | - Shuo-Yi Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Su-Xin Zhang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Xiao-Ming Liu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Lun-Xi Liang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410006, Hunan Province, China
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Guan JL, Xu TT, Lin Y, Mo YS, He BY, Han YY, Li JY, Xia SH, Zhou YN, Liao JZ, Li PY. High-dose dual therapy for Helicobacter pylori eradication inducing less impact on the gut microbiota. Gut Pathog 2025; 17:7. [PMID: 39885529 PMCID: PMC11783801 DOI: 10.1186/s13099-025-00682-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 01/23/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) eradication regimens may have different effects on the gut microbiota. Few studies have analyzed the safety of high-dose dual therapy (HDDT) from a micro-ecological perspective. This study aimed to compare the impact of H. pylori eradication with HDDT and bismuth quadruple therapy (BQT) on gut microbiota. PATIENTS AND METHODS H. Pylori-infected treatment-naive patients were recruited and screened from September 2023 to April 2024 and randomly assigned to the HDDT group (esomeprazole 20 mg, amoxicillin 750 mg, qid, 14 days) or BQT group (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 600 mg, bid, 14 days). Fresh stool specimens were collected and stored before treatment and at week 2 and week 8 after treatment. The diversity and composition of the gut microbiota were compared and analyzed in both groups using 16 S rRNA gene sequencing. RESULTS Forty-nine H. pylori positive patients were enrolled and randomly assigned to either the HDDT (n = 24) or the BQT group (n = 25) group. Compared with baseline, alpha and beta diversities significantly changed at week 2 after receiving BQT and did not recover fully at week 8. However, in the HDDT group, the diversities at week 2 changed mildly without statistical significance, compared to baseline. Additionally, a greater number of species had alterations in their abundances in the BQT group compared to the HDDT group at week 2. However, the abundances of these species were restored to their previous levels at week 8 in both the HDDT and BQT groups. CONCLUSIONS Compared to BQT, HDDT exerted less impact on the diversity and composition of the gut microbiota. CLINICAL TRIAL REGISTRATION ChiCTR2100053268.
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Affiliation(s)
- Jia-Lun Guan
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
| | - Ting-Ting Xu
- Department of Gastroenterology, Wenchang People's Hospital, Wenchang, China
| | - Ya Lin
- Department of Gastroenterology, Wenchang People's Hospital, Wenchang, China
| | - Yan-Shuai Mo
- Department of Anesthesiology, Wenchang People's Hospital, Wenchang, China
| | - Bi-Yu He
- Department of Gastroenterology, Wenchang People's Hospital, Wenchang, China
| | - Ying-Ying Han
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
| | - Ji-Yan Li
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
| | - Su-Hong Xia
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
| | - Ya-Ni Zhou
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
| | - Jia-Zhi Liao
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
| | - Pei-Yuan Li
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
- Department of Gastroenterology, Wenchang People's Hospital, Wenchang, China.
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Choi YS, Hwang JG, Kim JW, Min H, Seong CH, Hong SH, Kim NY, Park MK. Pharmacodynamics Between a Dual Delayed-Release Formulation of Low-Dose Esomeprazole and Famotidine in Healthy Korean Subjects. Clin Ther 2024; 46:622-628. [PMID: 39033046 DOI: 10.1016/j.clinthera.2024.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 06/17/2024] [Accepted: 06/17/2024] [Indexed: 07/23/2024]
Abstract
PURPOSE Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. METHODS This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FINDINGS The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. IMPLICATIONS Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis. CLINICALTRIALS gov identifier: NCT04967014.
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Affiliation(s)
- Young-Sim Choi
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheong-ju, Republic of Korea
| | - Jun Gi Hwang
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheong-ju, Republic of Korea
| | - Jae-Won Kim
- Chungbuk National University College of Medicine, Cheong-ju, Republic of Korea
| | - Hyojin Min
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheong-ju, Republic of Korea
| | - Chang-Hwan Seong
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheong-ju, Republic of Korea
| | - Sung Hee Hong
- Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea; Department of Pharmaceutical Medicine and Regulatory Science, Yonsei University, Seoul, Republic of Korea
| | - Na Young Kim
- Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea
| | - Min Kyu Park
- Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheong-ju, Republic of Korea.
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Jia J, Zhao H, Li F, Zheng Q, Wang G, Li D, Liu Y. Research on drug treatment and the novel signaling pathway of chronic atrophic gastritis. Biomed Pharmacother 2024; 176:116912. [PMID: 38850667 DOI: 10.1016/j.biopha.2024.116912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/10/2024] Open
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.
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Affiliation(s)
- Jinhao Jia
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Huijie Zhao
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Fangfei Li
- Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Special Administrative Region of China
| | - Qiusheng Zheng
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China
| | - Guoli Wang
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Defang Li
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China.
| | - Ying Liu
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China.
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Jiang X, Deng B, Gao X, Zhang Y, Li G, Li G, She Q, Ding Y. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen - An open-label, randomized trial. Open Med (Wars) 2023; 18:20230722. [PMID: 37465346 PMCID: PMC10350889 DOI: 10.1515/med-2023-0722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 04/23/2023] [Accepted: 05/12/2023] [Indexed: 07/20/2023] Open
Abstract
This research aimed to evaluate the eradication efficacy, safety, and gastrointestinal symptom relief rates of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy in primary eradication patients in Yangzhou, China. It also investigated the possible factors influencing the success of different Helicobacter pylori eradication regimens. A single-center, prospective, open-label, randomized controlled study was performed from December 2020 and October 2021, in which 255 patients with H. pylori infection were assigned in a 1:1:1 ratio to the three different groups. Our results showed that high-dose dual therapy (91.0%, 71/78) and resistance gene-based triple therapy (94.9%, 75/79) achieved eradication rates and compliance equivalent to those of empirical bismuth quadruple therapy (85.3%, 64/75) in the per-protocol analysis, while high-dose dual therapy had lower rates of adverse events (11.5%, 9/78, P < 0.05), fewer side effects, and greater safety. Most patients' gastrointestinal discomfort symptoms improved after eradication of H. pylori. Poor compliance (P < 0.05) and antibiotic resistance (P < 0.05) were risk factors for the efficacy of H. pylori eradication. Therefore, the appropriate regimen can be individualized for eradication therapy in clinical practice according to the patient's resistance and tolerance to the drug.
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Affiliation(s)
- Xin Jiang
- Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Bin Deng
- Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Xuefeng Gao
- Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Yun Zhang
- Department of Emergency Medicine, Suqian Hospital of Nanjing Drum Tower Hospital Group, Suqian, China
| | - Guangyao Li
- Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Guiqing Li
- Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Qiang She
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Yanbing Ding
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
- Institute of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
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Tai WC, Yang SC, Yao CC, Wu CK, Liu AC, Lee CH, Kuo YH, Chuah SK, Liang CM. The Efficacy and Safety of 14-day Rabeprazole Plus Amoxicillin High Dose Dual Therapy by Comparing to 14-day Rabeprazole-Containing Hybrid Therapy for the Naïve Helicobacter pylori Infection in Taiwan: A Randomized Controlled Trial. Infect Dis Ther 2023; 12:1415-1427. [PMID: 37133673 PMCID: PMC10229508 DOI: 10.1007/s40121-023-00811-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/14/2023] [Indexed: 05/04/2023] Open
Abstract
INTRODUCTION High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies. METHODS In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later. RESULTS The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis. CONCLUSION This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.
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Affiliation(s)
- Wei-Chen Tai
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Shih-Cheng Yang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
| | - Chih-Chien Yao
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
| | - Cheng-Kun Wu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
| | - An-Che Liu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
| | - Chen-Hsiang Lee
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
- Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan
- Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan.
- Chang Gung University College of Medicine, Taoyuan City, Taiwan.
| | - Chih-Ming Liang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833, Taiwan.
- Chang Gung University College of Medicine, Taoyuan City, Taiwan.
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Macedo Silva V, Lima Capela T, Freitas M, Boal Carvalho P, Magalhães J, Cotter J. A "new" option in Helicobacter pylori eradication: High-dose amoxicillin dual therapy outperforms bismuth quadruple therapy in a high dual resistance setting. Helicobacter 2023; 28:e12962. [PMID: 36828647 DOI: 10.1111/hel.12962] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/12/2023] [Accepted: 02/15/2023] [Indexed: 02/26/2023]
Abstract
BACKGROUND Currently, bismuth quadruple therapy (BQT) is indicated as a first-line treatment for Helicobacter pylori eradication in areas with high dual metronidazole and clarithromycin resistance, with its use being limited by its low tolerability and significant cost. A novel regimen with high-dose amoxicillin dual therapy (HDADT) has emerged as an alternative. The aim of this study was to compare the results of these two treatments on HP eradication. MATERIALS AND METHODS Prospective randomized study including 100 consecutive patients undergoing H. pylori eradication. Each patient was randomized (in a 1:1 ratio) to one group of treatment: BQT (bismuth 140 mg + metronidazole 125 mg + tetracycline 125 mg, four times a day, for 10 days) or HDADT (amoxicillin 1000 mg alternating with amoxicillin 500 mg, four times a day, for 14 days), both associated with esomeprazole 40 mg twice a day. The primary aim was to compare treatments' efficacies. Secondary aims were to assess symptoms persistence and tolerability. RESULTS A total of 100 patients were included, 54% women, with a mean age of 55 ± 14 years. From these, five were lost to follow-up. Effective eradication proven by negative stool antigen test was significantly higher in patients randomized to HDADT when compared to BQT for both intention-to-treat (ITT) (96.2% vs. 81.4%; p = .022) and per-protocol (PP) (95.9% vs. 81%; p = .025) analysis. These differences were even more pronounced when only considering second line treatment (100% vs. 62.5%; p = .028). Side effects did not differ significantly between BQT and HDADT groups for both ITT (7.0% vs. 2.0%; p = .254) and PP (4.8% vs. 0%; p = .210) analysis. CONCLUSIONS When compared to BQT, treatment with HDADT presented higher and near 100% efficacy in eradicating H. pylori, without differences in reported side effects or compliance. This treatment represents an important alternative for populations with increasing incidences of resistance to the currently recommended antibiotic regimens.
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Affiliation(s)
- Vítor Macedo Silva
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - Tiago Lima Capela
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - Marta Freitas
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - Pedro Boal Carvalho
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - Joana Magalhães
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
| | - José Cotter
- Gastroenterology Department, Hospital da Senhora da Oliveira, Guimarães, Portugal.,Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal
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Zhou BG, Mei YZ, Zhang M, Jiang X, Li YY, Ding YB. High-dose dual therapy versus bismuth-containing quadruple therapy for Helicobacter pylori eradication: a systematic review and meta-analysis with trial sequential analysis. Therap Adv Gastroenterol 2023; 16:17562848221147756. [PMID: 36644129 PMCID: PMC9837272 DOI: 10.1177/17562848221147756] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 12/11/2022] [Indexed: 01/12/2023] Open
Abstract
Background and objective Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT. Design A systematic review and meta-analysis was conducted. Methods PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness. Results A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive. Conclusions Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori, with fewer adverse effects and similar compliance. Registration Open Science Framework registries (No: osf.io/th4vd).
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Affiliation(s)
- Ben-Gang Zhou
- Dalian Medical University, Dalian, Liaoning Province, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Yu-Zhou Mei
- Department of Gastroenterology, The People’s Hospital of China Three Gorges University, Yichang, Hubei Province, China
| | - Min Zhang
- Public Health Institute of Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu Province, China
| | - Xin Jiang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
- Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Yao-Yao Li
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
| | - Yan-Bing Ding
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
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9
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Shen C, Li C, Lv M, Dai X, Gao C, Li L, Zhang Q, Pan W, Liu C, Han S, Zhang Y, Ding S, Deng H, Yao Y, Xu J, Wei M, Shi H, Yuan P, Yang X, Jian Y, Shan J, Liu Y, Chen Z, Deng X, Liu F, Deng L, Zhong X, Li H, He S, Chen L, Liu G, Xu H, Zhong Y, Shi H, Ren J. The prospective multiple-centre randomized controlled clinical study of high-dose amoxicillin-proton pump inhibitor dual therapy for H. pylori infection in Sichuan areas. Ann Med 2022; 54:426-435. [PMID: 35098820 PMCID: PMC8812792 DOI: 10.1080/07853890.2022.2031269] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. METHODS A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. RESULTS There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p<.01)). CONCLUSIONS For the initial treatment of H. pylori infection, the high-dose dual therapy regimen has the same efficacy as the bismuth-containing quadruple therapy regimen, good compliance, less adverse reactions and high safety, so it can be recommended as the empirical first-line treatment regimen for the eradication of H. pylori (KY2019173).
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Affiliation(s)
- Cheng Shen
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Changping Li
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Muhan Lv
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiaosong Dai
- Sichuan Provincial People's Hospital, Chengdu, China
| | - Caiping Gao
- Sichuan Provincial People's Hospital, Chengdu, China
| | - Liangping Li
- Sichuan Provincial People's Hospital, Chengdu, China
| | - Qin Zhang
- First People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, China
| | - Wen Pan
- Sichuan University West China Hospital Tibet People's Government in Chengdu Office Branch, Chengdu, China
| | - Chao Liu
- Sichuan University West China Hospital Tibet People's Government in Chengdu Office Branch, Chengdu, China
| | - Sijing Han
- Chengdu Medical College Second Affiliated Hospital, Chengdu, China
| | - Yang Zhang
- Chengdu Medical College Second Affiliated Hospital, Chengdu, China
| | | | - Hong Deng
- People's Hospital of Deyang City, Deyang, China
| | - Yong Yao
- Suining Central Hospital, Suining, China
| | - Jianyu Xu
- Suining Central Hospital, Suining, China
| | | | - Haiyan Shi
- Bazhong Central Hospital, Bazhong, China
| | - Peijie Yuan
- The Fourth People's Hospital of GuangYuan, GuangYuan, China
| | - Xiaoyan Yang
- Chengdu Second People's Hospital, Chengdu, China
| | - Yi Jian
- Chengdu Second People's Hospital, Chengdu, China
| | - Jing Shan
- Chengdu Third People's Hospital, Chengdu, China
| | - Yan Liu
- Chengdu Fifth People's Hospital, Chengdu, China
| | - Zonghua Chen
- The Second People's Hospital of Yibin, West China Hospital of Sichuan University, Yibin, China
| | | | - Fei Liu
- Leshan City Geriatric Hospital, Leshan, China
| | - Lijuan Deng
- Leshan Sichuan Armed Police General Hospital, Leshan, China
| | - Xianfei Zhong
- Leshan Sichuan Armed Police General Hospital, Leshan, China
| | - Hong Li
- Pengzhou People's Hospital, Chengdu, China
| | - Shaoya He
- Sichuan Anyue County People's Hospital, Ziyang, China
| | - Li Chen
- Sichuan Anyue County People's Hospital, Ziyang, China
| | - Gang Liu
- Zigong Third People's Hospital, Zigong, China
| | - Hairong Xu
- Zigong Third People's Hospital, Zigong, China
| | - Yuquan Zhong
- First Peoples Hospital of Neijiang, Neijiang, China
| | - Hua Shi
- The First People's Hospital of Ziyang, Ziyang, China
| | - Jiangang Ren
- Wuhou District Third People's Hospital, Chengdu, China
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10
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Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 572] [Impact Index Per Article: 190.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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11
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Guan JL, Hu YL, An P, He Q, Long H, Zhou L, Chen ZF, Xiong JG, Wu SS, Ding XW, Luo HS, Li PY. Comparison of high-dose dual therapy with bismuth-containing quadruple therapy in Helicobacter pylori-infected treatment-naive patients: An open-label, multicenter, randomized controlled trial. Pharmacotherapy 2022; 42:224-232. [PMID: 35075679 DOI: 10.1002/phar.2662] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/21/2021] [Accepted: 11/23/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.
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Affiliation(s)
- Jia-Lun Guan
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yun-Lian Hu
- Department of Gastroenterology, Hubei University of Chinese Medicine, Wuhan, China
| | - Ping An
- Department of Gastroenterology, Wuhan University People's Hospital, Wuhan, China
| | - Qiong He
- Department of Gastroenterology, Wuhan Red Cross Hospital, Wuhan, China
| | - Hui Long
- Department of Gastroenterology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Lin Zhou
- Department of Gastroenterology, Suizhou Central Hospital, Wuhan, China
| | - Zhi-Fen Chen
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jian-Guang Xiong
- Department of Gastroenterology, Xianning Central Hospital, Wuhan, China
| | - Shi-Sheng Wu
- Department of Gastroenterology, The Second Hospital of Huangshi, Wuhan, China
| | - Xiang-Wu Ding
- Department of Gastroenterology, Wuhan Puai Hospital, Wuhan, China
| | - He-Sheng Luo
- Department of Gastroenterology, Wuhan University People's Hospital, Wuhan, China
| | - Pei-Yuan Li
- Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Gastroenterology, Wenchang People's Hospital, Hainan, China
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12
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Shiotani A, Roy P, Lu H, Graham DY. Helicobacter pylori diagnosis and therapy in the era of antimicrobial stewardship. Therap Adv Gastroenterol 2021; 14:17562848211064080. [PMID: 34987609 PMCID: PMC8721397 DOI: 10.1177/17562848211064080] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/15/2021] [Indexed: 02/04/2023] Open
Abstract
The diagnosis and therapy of Helicobacter pylori infection have undergone major changes based on the use the principles of antimicrobial stewardship and increased availability of susceptibility profiling. H. pylori gastritis now recognized as an infectious disease, as such there is no placebo response allowing outcome to be assessed in relation to the theoretically obtainable cure rate of 100%. The recent recognition of H. pylori as an infectious disease has changed the focus to therapies optimized to reliably achieve high cure rates. Increasing antimicrobial resistance has also led to restriction of clarithromycin, levofloxacin, or metronidazole to susceptibility-based therapies. Covid-19 resulted in the almost universal availability of polymerase chain reaction testing in hospitals which can be repurposed to utilize readily available kits to provide rapid and inexpensive detection of clarithromycin resistance. In the United States, major diagnostic laboratories now offer H. pylori culture and susceptibility testing and American Molecular Laboratories offers next-generation sequencing susceptibility profiling of gastric biopsies or stools for the six commonly used antibiotics without need for endoscopy. Current treatment recommendations include (a) only use therapies that are reliably highly effective locally, (b) always perform a test-of-cure, and (c) use that data to confirm local effectiveness and share the results to inform the community regarding which therapies are effective and which are not. Empiric therapy should be restricted to those proven highly effective locally. The most common choices are 14-day bismuth quadruple therapy and rifabutin triple therapy. Prior guidelines and treatment recommendations should only be used if proven locally highly effective.
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Affiliation(s)
- Akiko Shiotani
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Priya Roy
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hong Lu
- GI Division, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA
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13
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Li C, Shi Y, Suo B, Tian X, Zhou L, Song Z. PPI-amoxicillin dual therapy four times daily is superior to guidelines recommended regimens in the Helicobacter pylori eradication therapy within Asia: A systematic review and meta-analysis. Helicobacter 2021; 26:e12816. [PMID: 34002433 DOI: 10.1111/hel.12816] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/17/2021] [Accepted: 04/19/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Systematic reviews suggested that the eradication efficacy of PPI-amoxicillin dual therapy is similar to that of other commonly used regimens. However, it might be affected by the medication frequency. Basic and clinical studies have shown that dual therapy administered four-times daily has a reliable pathophysiological basis and could achieve satisfactory efficacy. Therefore, a systematic review of RCTs of dual therapy and other regimens was conducted to clarify whether dual therapy is superior to guidelines recommended regimens. MATERIALS AND METHODS The RCTs comparing dual therapy with other regimens were subjected to meta-analysis to evaluate the eradication rate, adverse reactions, and compliance using a random-effects model. RESULTS Dual therapy administered four-times daily had a higher eradication rate than other regimens (intention-to-treat analysis: 89.7% vs 84.6%, OR: 1.52, 95%CI 1.08-2.14, p = 0.02; per-protocol analysis: 92.6% vs 88.2%, OR: 1.54, 95%CI 1.01-2.34, p = 0.04). In first-line therapy, according to intention-to-treat analysis, the eradication rate of dual therapy was higher than other regimens (89.8% vs 84.2%, OR: 1.63, 95%CI 1.02-2.61, p = 0.04). In per-protocol analysis, dual therapy showed better efficacy than others (92.9% vs 88.3%, OR: 1.68, 95% CI 0.98-2.89, p = 0.06), but not significantly. In salvage treatment, no significant difference was detected. The safety of dual therapy was significantly better than other regimens (19.6% vs 36.7%, p < 0.01), but no difference was observed in compliance (p = 0.58). CONCLUSION PPI-amoxicillin dual therapy administered four-times daily has better efficacy and safety in H. pylori eradication than current guidelines recommended regimens, especially in first-line therapy, and mainly in Asia.
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Affiliation(s)
- Cailing Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yanyan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Baojun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xueli Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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14
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Hu CT. High-dose dual therapy versus bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection – A review of the strengths, weaknesses, and proposed solutions. Tzu Chi Med J 2021; 34:303-309. [PMID: 35912055 PMCID: PMC9333101 DOI: 10.4103/tcmj.tcmj_185_21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/19/2021] [Accepted: 08/17/2021] [Indexed: 11/04/2022] Open
Abstract
Helicobacter pylori is the principal cause of peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. The first treatment to H. pylori infection is dual therapy (a bismuth compound plus metronidazole). On the launch of omeprazole in 1988, dual therapy became omeprazole and amoxicillin (low dose). The poor H. pylori eradication rates by either bismuth-based or low-dose dual therapy drove more combinations of antibiotics were needed. Antibiotic resistance, especially clarithromycin and metronidazole, has made bismuth-containing quadruple therapy (BCQT) a savior for first-line and second-line treatments. However, its complicated dosing regimen commonly causes more adverse events and poor drug compliance. Thus, high-dose dual therapy (HDDT) has been re-arising. This article reviews the strengths and weaknesses of HDDT versus BCQT with proposed solutions.
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15
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Song Z, Zhou L, Xue Y, Suo B, Tian X, Niu Z. A comparative study of 14-day dual therapy (esomeprazole and amoxicillin four times daily) and triple plus bismuth therapy for first-line Helicobacter pylori infection eradication: A randomized trial. Helicobacter 2020; 25:e12762. [PMID: 33040439 DOI: 10.1111/hel.12762] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Favorable outcomes in treating H pylori infection using "dual therapy (proton pump inhibitor and amoxicillin four times daily)" have attracted widespread attention. However, there are few reports, and the study results lack agreement. This study aimed to compare the eradication rate, safety, and compliance of naïve-treatment patients with H pylori infection on "dual therapy" with those on "triple plus bismuth (TPB) therapy." METHODS This is a non-inferior randomized controlled trial conducted on 760 patients with H pylori infection. The participants were randomly assigned to two eradication groups: dual therapy (esomeprazole 20 mg and amoxicillin 750 mg four times daily) and TPB therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily) for 14 days. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed about 8 weeks after eradication to evaluate outcome. Antibiotic resistance and CYP2C19 polymorphism were determined. RESULTS Compared with TPB therapy, dual therapy had significantly higher eradication rates in intention-to-treat (87.1% vs 80.5%, rate difference 6.6%), modified intention-to-treat (90.9% vs 85.5%, 5.5%) and per-protocol (92.4% vs 87.8%, 4.7%) analyses, respectively. Adverse reactions in dual therapy group were significantly lower than TPB therapy group (17.6% vs 25.5%, P = .008), and dual therapy group had better compliance (96.3% vs 92.3%, P = .019). Antibiotic resistance and poor compliance were also associated with treatment failure. CONCLUSIONS Dual therapy (esomeprazole and amoxicillin four times daily) was non-inferior to, and even superior to TPB therapy as first-line H pylori eradication.
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Affiliation(s)
- Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yan Xue
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Baojun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xueli Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhanyue Niu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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16
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Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors. Pharmacol Res 2020; 152:104606. [DOI: 10.1016/j.phrs.2019.104606] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 12/13/2019] [Accepted: 12/13/2019] [Indexed: 02/06/2023]
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17
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Gao CP, Xiao X, Liu PX, Zhou Z, Li LP, Han SX. High-dose amoxicillin/esomeprazole dual therapy as a first-line therapy for Helicobacter pylori eradication. Shijie Huaren Xiaohua Zazhi 2018; 26:353-359. [DOI: 10.11569/wcjd.v26.i6.353] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical efficacy and safety of high-dose amoxicillin/esomeprazole dual therapy as a first-line therapy for Helicobacter pylori (H. pylori) eradication.
METHODS One hundred and forty-two subjects infected with H. pylori and naive to treatment were randomly assigned to receive either 14-d high-dose amoxicillin/esomeprazole dual therapy (esomeprazole 20 mg and amoxicillin 0.75 g, four times a day; EA group) or bismuth-based quadruple therapy [esomeprazole 20 mg, bismuth potassium citrate 220 mg (elemental bismuth), amoxicillin 1 g, and clarithromycin 0.5 g, twice a day; EBAC group]. Six weeks after treatment, H. pylori eradication was assessed by using the urea breath test (13C or 14C).
RESULTS A total of 131 subjects completed this clinical trial. H. pylori eradication rates by intention-to-treat (ITT) and per-protocol (PP) analysis in the EA group were 82.9% and 89.2%, respectively, and those in the EBAC group were 86.1% and 93.9%, respectively. No significant difference was found in H. pylori eradication rates by both ITT and PP analysis (P > 0.05). The incidence of side effects by PP analysis in the EBAC group was significantly higher than that in the EA group (15.2% vs 3.1%, P < 0.05). All the side effects disappeared after discontinuing the drugs.
CONCLUSION High-dose amoxicillin/esomeprazole dual therapy can be used as an effective and safety first-line therapy for H. pylori infection.
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Abstract
OBJECTIVE The aim of this study was to evaluate the efficacy/tolerability of a culture-guided approach in the eradication of Helicobacter pylori and identify factors associated with antibiotic resistance/treatment failure. PATIENTS AND METHODS This retrospective single-center study included patients who underwent culture-guided treatment for H. pylori infection, after two ineffective eradication attempts, between October 2012 and December 2016. We assessed the following demographic and clinical data of the patients: sex, age, BMI, alcohol and tobacco consumption, history of dyspepsia, peptic ulceration and first-degree relatives with gastric cancer, antibiotic susceptibility results, treatment composition, tolerability, and success. The treatment success was confirmed by a monoclonal stool antigen test. RESULTS Culture-guided treatment was performed in 42 patients (57% women, mean age±SD: 48.9±11.4 years). The rates of antibiotic resistance were as follows: clarithromycin 86%, metronidazole 67%; levofloxacin 52%, tetracycline 2%, and amoxicillin and rifampicin 0%. Double resistance to clarithromycin and metronidazole was found in 59.5% of the patients. Most patients showed resistance to less than three antibiotics, but 31% were resistant to three or more. Intention-to-treat and per-protocol eradication rates were 59.5 and 61.5%. Adverse events occurred in 15 (35.7%) patients, but only two (4.8%) patients did not complete treatment because of adverse events. Only age more than 50 years was associated with resistance to three or more antibiotics. Having a first-degree relative with gastric cancer was associated with treatment failure and having a BMI of at least 25 kg/m protected from failure. CONCLUSION Third-line culture-guided treatment often fails to eradicate H. pylori infection. We need to find factors other than in-vitro antibiotic resistance to explain these suboptimal results.
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Ichikawa H, Sugimoto M, Sugimoto K, Andoh A, Furuta T. Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis. J Gastroenterol Hepatol 2016; 31:716-26. [PMID: 26580676 DOI: 10.1111/jgh.13233] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 08/14/2015] [Accepted: 11/10/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are mainly metabolized by cytochrome P450 2C19 (CYP2C19) and used as the first-line therapy for gastroesophageal reflux disease (GERD). However, while several studies have examined the influence of CYP2C19 polymorphism on GERD treatment with PPIs, most have had small sample sizes and were conducted in a single center. Here, we used meta-analysis to investigate whether or not the CYP2C19 rapid metabolizer (RM) genotype is a risk factor for GERD patients being refractory to PPI therapy. METHODS PubMed and other electronic databases were systematically searched up to August 2014 using the following terms: "GERD and CYP2C19", "esophagitis and CYP2C19", and "non-erosive reflux disease and CYP2C19." Searches were limited to publications in English, and two investigators evaluated eligible studies and extracted data. RESULTS The total efficacy rate of PPIs for GERD, including reflux esophagitis (RE) and non-erosive reflux disease, was 56.4% (95% confidence interval [CI]; 53.9-58.9%, 870/1543) in intention-to-treat analysis and 63.8% (95%CI; 61.3-66.2%, 950/1489) in per-protocol analysis. Efficacy rates varied significantly between CYP2C19 genotypes (intention-to-treat analysis: RMs, 52.2% [315/604]; intermediate metabolizers, 56.7% [298/526]; poor metabolizers [PMs], 61.3% [138/225]; P = 0.047). Among RE patients, CYP2C19 RMs had an increased risk of being refractory to PPI therapy compared with PMs (odds ratio: 1.661, 95% CI: 1.023-2.659, P = 0.040). CONCLUSIONS The present meta-analysis demonstrates that CYP2C19 RMs with RE have an increased risk of being refractory to PPI therapy compared with PMs. Individualized dosing regimen with PPIs based on CYP2C19 genotype might be a valid therapeutic strategy for overcoming insufficient gastric acid inhibition.
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Affiliation(s)
- Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.,Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Kagami T, Sugimoto M, Ichikawa H, Sahara S, Uotani T, Yamade M, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Miyajima H, Furuta T. One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19. Eur J Clin Pharmacol 2015; 71:1467-75. [PMID: 26427705 DOI: 10.1007/s00228-015-1941-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/04/2015] [Indexed: 11/24/2022]
Abstract
BACKGROUND Four times daily dosing (qid) with a proton pump inhibitor can cause rapid increase in intragastric pH. We investigated the efficacy of the front-loading with rabeprazole 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19. METHODS Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg bid regimen only. Twenty-four-hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h median intragastric pHs on days 1, 4, and 7. RESULTS Twenty-four-hour intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9, and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH·day) was significantly higher than that in EMs with rabeprazole 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4). CONCLUSIONS The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.
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Affiliation(s)
- Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shu Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahiro Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Moriya Iwaizumi
- Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hiroaki Miyajima
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
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21
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Scarpignato C, Hunt RH. Editorial: towards extended acid suppression--the search continues. Aliment Pharmacol Ther 2015; 42:1027-9. [PMID: 26374257 DOI: 10.1111/apt.13384] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- C Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Parma, Italy.
| | - R H Hunt
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada
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