Amoxicillin high-dose dual therapy for Helicobacter pylori primary eradication: Proton pump inhibitor and potassium-competitive acid blocker, which’s better?

Table 1 Baseline characteristics of patients, n (%)

Baseline factors	Total (n = 439)	14d-EA group (n = 221)	14d-B-quadruple group (n = 218)	P value1	Total (n = 367)	14d-VA group (n = 183)	14d-VAC group (n = 184)	P value2
Sex (male/female)	196/243	100/121	96/122	0.798	171/196	83/100	88/96	0.635
Age (years)	41.14 ± 12.07	41.05 ± 11.88	41.22 ± 12.29	0.879	43.04 ± 13.19	42.38 ± 13.60	43.69 ± 12.77	0.341
Fixed occupation (no/yes)	163/276 (62.87)	79/142 (64.25)	84/134 (61.47)	0.546	145/222 (60.49)	70/113 (61.75)	75/109 (59.24)	0.623
Ethnic group (Han/others)	420/19 (95.67)	211/10 (95.48)	209/9 (95.87)	0.838	349/18 (95.10)	175/8 (95.63)	174/10 (94.57)	0.637
BMI (kg/m²)	22.85 ± 2.74	22.94 ± 2.74	22.76 ± 2.75	0.493	22.77 ± 2.98	22.58 ± 2.88	22.97 ± 3.07	0.206
BSA (m²)	1.65 ± 0.16	1.65 ± 0.16	1.65 ± 0.16	0.777	1.63 ± 0.18	1.63 ± 0.18	1.63 ± 0.18	0.672
Native place (human/others)	378/61 (86.10)	193/28 (87.33)	185/33 (84.86)	0.455	315/52 (85.83)	159/24 (86.89)	156/28 (84.78)	0.564
Education status (primary/junior high school/high school/college/above university)	33/ 56/74/208/68	13/29/42/105/32	20/27/32/103/36	0.534	29/47/62/171/58	11/24/29/83/36	18/23/33/88/22	0.240
Place of residence (urban area/suburban area/rural area)	360/49/30	180/23/18	180/26/12	0.506	301/41/25	150/18/15	151/23/10	0.447
Smoking (no/yes)	329/110 (25.06)	161/60 (27.15)	168/50 (22.94)	0.308	282/85 (23.16)	136/47 (25.68)	146/38 (20.65)	0.253
Drinking (none/occasional/frequent)	301/115/23	153/57/11	148/58/12	0.944	252/96/19	126/46/11	126/50/8	0.727
Past medical history (no/yes)	371/68 (15.49)	188/33 (14.93)	183/35 (16.06)	0.745	308/59 (16.08)	154/29 (15.85)	154/30 (16.30)	0.905
Family infection of H. pylori (no/Yes/undetected)	172/138/129	86/71/64	86/67/65	0.950	144/115/108	71/59/53	73/56/55	0.932

¹P values were obtained from two-sided comparisons of difference between the 14d-EA group and the 14d-B-quadruple group.

²P values were obtained from two-sided comparisons of difference between the 14d-VA group and the 14d-VAC group.

BMI: Body mass index; BSA: Body surface area; EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth; VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.

Table 2 Digestive symptoms and endoscopy diagnosis of patients, n (%)

Baseline factors	Total (n = 439)	14d-EA group (n = 221)	14d-B-quadruple group (n = 218)	P value1	Total (n = 367)	14d-VA group (n = 183)	14d-VAC group (n = 184)	P value2
Digestive symptoms (no/yes)	102/337 (76.77)	56/165 (74.66)	46/172 (78.90)	0.293	75/292 (79.56)	43/140 (76.50)	32/152 (82.61)	0.147
Epigastric distension (no/yes)	303/136 (30.98)	156/65 (29.41)	147/71 (32.57)	0.474	236/131 (35.69)	122/61 (33.33)	114/70 (38.04)	0.346
Sour regurgitation (no/yes)	344/95 (21.64)	171/50 (22.62)	173/45 (20.64)	0.614	268/99 (26.98)	139/44 (24.04)	129/55 (29.89)	0.207
Belching (no/yes)	357/82 (18.68)	182/39 (17.65)	175/43 (19.72)	0.577	307/60 (16.35)	151/32 (17.49)	156/28 (15.22)	0.557
Hiccup (no/yes)	389/50 (11.39)	202/19 (8.60)	187/31 (14.22)	0.064	331/36 (9.81)	167/16 (8.74)	164/20 (10.87)	0.493
Epigastric pain (no/yes)	290/149 (33.94)	146/75 (33.94)	144/74 (33.94)	0.999	230/137 (37.33)	116/67 (36.61)	114/70 (38.04)	0.777
Nausea (no/yes)	386/53 (12.07)	194/27 (12.22)	192/26 (11.93)	0.926	320/47 (12.81)	163/20 (10.93)	157/27 (14.67)	0.283
Vomiting (no/yes)	417/22 (5.01)	210/11 (4.98)	207/11 (5.05)	0.974	352/15 (4.09)	173/10 (5.46)	179/5 (2.72)	0.184
Hematemesis (no/yes)	438/1 (0.23)	221/0 (0.00)	217/1 (0.46)	0.497	367/0 (0.00)	183/0 (0.00)	184/0 (0.00)
Tarry stool (no/yes)	432/7 (1.59)	217/4 (1.81)	215/3 (1.38)	1.000	358/9 (2.45)	178/5 (2.73)	180/4 (2.17)	0.993
Emaciation (no/yes)	427/12 (2.73)	218/3 (1.36)	209/9 (4.13)	0.075	359/8 (2.18)	178/5 (2.73)	181/3 (1.63)	0.715
Halitosis (no/yes)	290/149 (33.94)	153/68 (30.77)	137/81 (37.16)	0.158	249/118 (32.15)	126/57 (31.15)	123/61 (33.15)	0.681
Others (no/yes)	419/20 (4.56)	208/13 (5.88)	211/7 (3.21)	0.180	321/46 (12.53)	158/25 (13.66)	163/21 (11.41)	0.515
Endoscopy diagnosis (no/yes)	140/299 (68.11)	68/153 (69.23)	72/146 (66.97)	0.612	122/245 (66.76)	64/119 (65.03)	58/126 (68.48)	0.483
Atrophic gastritis (no/yes)	358/81 (18.45)	178/43 (19.46)	180/38 (17.43)	0.584	300/67 (18.26)	152/31 (16.94)	148/36 (19.57)	0.515
Non-atrophic gastritis (no/yes)	257/182 (41.46)	126/95 (42.99)	131/87 (39.91)	0.513	222/145 (39.51)	113/70 (38.25)	109/75 (40.76)	0.623
Gastric ulcer (no/yes)	378/61 (13.90)	185/36 (16.29)	193/25 (11.47)	0.144	322/45 (12.26)	159/24 (13.11)	163/21 (11.41)	0.619
Duodenobulbar ulcer (no/yes)	389/50 (11.39)	195/26 (11.76)	194/24 (11.01)	0.803	324/43 (11.72)	159/24 (13.11)	165/19 (10.33)	0.406
Gastritis verrucosa (no/yes)	430/9 (2.05)	216/5 (2.26)	214/4 (1.83)	1.000	361/6 (1.63)	180/3 (1.64)	181/3 (1.63)	1.000
Erosive gastritis (no/yes)	373/66 (15.03)	194/27 (12.22)	179/39 (17.89)	0.096	306/61 (16.62)	149/34 (18.58)	157/27 (14.67)	0.315
Bile reflux gastritis (no/yes)	410/29 (6.61)	205/16 (7.24)	205/13 (5.96)	0.590	341/26 (7.08)	167/16 (8.74)	174/10 (5.43)	0.217
Others (no/yes)	422/17 (3.87)	212/9 (4.07)	210/8 (3.67)	0.827	348/19 (5.18)	170/13 (7.10)	178/6 (3.26)	0.097
History of antibiotics use in 2 years (no/yes)	213/226 (51.48)	114/107 (48.42)	99/119 (54.59)	0.196	175/192 (52.32)	96/87 (47.54)	79/105 (57.07)	0.068

¹P values were obtained from two-sided comparisons of difference between the 14d-EA group and the 14d-B-quadruple group.

²P values were obtained from two-sided comparisons of difference between the 14d-VA group and the 14d-VAC group.

EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth; VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.

Table 3 Eradication rates of each treatment group

Analysis	14d-EA group	14d-B-quadruple group	Difference from 14d-B-quadruple group (adjusted 95%CI for difference)	P value for difference1	P value for non-inferiority2	14d-VA group	14d-VAC group	Difference from 14d-VAC group (adjusted 95%CI for difference)	P value for difference3	P value for non-inferiority4
ITT (%)	70.59 (156/221)	83.49 (182/218)	-12.90 [-20.67, -5.13]	0.001a	0.7676	84.15 (154/183)	83.15 (153/184)	1.00 [-6.56, 8.57]	0.795	0.0022b
95%CI (%)	64.53-76.64	78.52-88.45				78.81-89.49	77.69-88.61
mITT (%)	92.86 (156/168)	98.38 (182/185)	-5.52 [-9.82, -1.22]	0.01a	0.0206b	96.25 (154/160)	92.73 (153/165)	3.52 [-1.41, 8.46]	0.165	< 0.0001b
95%CI (%)	88.92-96.79	96.54-100.00				93.27-99.23	88.72-96.73
PP (%)	93.94 (155/165)	98.38 (182/185)	-4.44 [-8.51, - 0.37]	0.028a	0.0037 b	96.75 (149/154)	93.75 (150/160)	3.00 [-1.68, 7.68]	0.212	< 0.0001b
95%CI (%)	90.26-97.62	96.54-100.00				93.92-99.58	89.96-97.54

¹P values were obtained from two-sided comparisons of the difference between the 14d-EA group and the 14d-B-quadruple group.

²P values were obtained from one-sided test comparisons of non-inferiority between the 14d-EA group and the 14d-B-quadruple group.

³P values were obtained from two-sided comparisons of the difference between the 14d-VA group and the 14d-VAC group.

⁴P values were obtained from one-sided test comparisons of non-inferiority between the 14d-VA group and the 14d-VAC group.

^aP < 0.05.

^bP < 0.025.

ITT: Intention-to-treat; mITT: Modified intention-to-treat; PP: Per-protocol; EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth; VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.

Table 4 Adverse events, compliance and relief of symptoms in the 14d-EA group and the 14d-B-quadruple group, n (%)

Adverse events, compliance and relief of symptoms	Total (n = 439)	14d-EA group (n = 221)	14d-B-quadruple group (n = 218)	P value
Patients with adverse events (yes/no)	30/409 (6.83)	11/210 (4.98)	19/199 (8.72)	0.121
Variety of adverse events
Changes in bowel habits (yes/no)	7/432 (1.59)	2/219 (0.90)	5/213 (2.29)	0.435
Skin rash (yes/no)	5/434 (1.14)	3/218 (1.36)	2/216 (0.92)	1.000
Bitter taste in mouth (yes/no)	5/434 (1.14)	0/221 (0.00)	5/213 (2.29)	0.070
Abdominal discomfort (yes/no)	5/434 (1.14)	2/219 (0.90)	3/215 (1.38)	0.988
Nausea (yes/no)	3/436 (0.68)	0/221 (0.00)	3/215 (1.38)	0.242
Poor appetite (yes/no)	3/436 (0.68)	2/219 (0.90)	1/217 (0.46)	1.000
Dizziness (yes/no)	2/437 (0.46)	2/219 (0.90)	0/218 (0.00)	0.499
Others (yes/no)	5/434 (1.14)	1/220 (0.45)	4/214 (1.83)	0.360
Discontinued drugs because of adverse events (yes/no)	4/435 (0.91)	1/220 (0.45)	3/215 (1.38)	0.606
Good compliance (yes/no)	432/7 (98.41)	217/4 (98.19)	215/3 (98.62)	1.000
Relief of symptoms (yes/no)	322/15 (n = 337) (95.55)	156/9 (n = 165) (94.55)	166/6 (n = 172) (96.51)	0.382

P values were obtained from two-sided comparisons of difference between the 14d-EA group and the 14d-B-quadruple group. EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth.

Table 5 Adverse events, compliance and relief of symptoms in the 14d-VA group and the 14d-VAC group, n (%)

Adverse events, compliance and relief of symptoms	Total (n = 367)	14d-VA group (n = 183)	14d-VAC group (n = 184)	P value
Patients with adverse events (yes/no)	39/328 (10.63)	18/165 (9.84)	21/163 (11.41)	0.624
Variety of adverse events
Abdominal discomfort (yes/no)	10/357 (2.72)	3/180 (1.64)	7/177 (3.80)	0.341
Nausea/vomiting (yes/no)	8/359 (2.18)	4/179 (2.19)	4/180 (2.17)	1.000
Bitter taste in mouth (yes/no)	7/360 (1.91)	3/180 (1.64)	4/180 (2.17)	1.000
Diarrhea (yes/no)	7/360 (1.91)	4/179 (2.19)	3/181 (1.63)	0.994
Sour regurgitation/heartburn (yes/no)	5/362 (1.36)	2/181 (1.09)	3/181 (1.63)	1.000
Dry mouth (yes/no)	4/363 (1.09)	2/181 (1.09)	2/182 (1.09)	1.000
Constipation (yes/no)	3/364 (0.82)	1/182 (0.55)	2/182 (1.09)	1.000
Poor appetite (yes/no)	3/364 (0.82)	2/181 (1.09)	1/183 (0.54)	0.996
Dizziness/fatigue (yes/no)	3/364 (0.82)	1/182 (0.55)	2/182 (1.09)	1.000
More saliva (yes/no)	2/365 (0.54)	1/182 (0.55)	1/183 (0.54)	1.000
Others (yes/no)	4/363 (1.09)	1/182 (0.55)	3/181 (1.63)	0.619
Discontinued drugs because of adverse events (yes/no)	3/364 (0.82)	2/181 (1.09)	1/183 (0.54)	0.996
Good compliance (yes/no)	353/14 (96.19)	175/8 (95.63)	178/6 (96.74)	0.579
Relief of symptoms (yes/no)	272/20 (n = 292) (93.15)	129/11 (n = 140) (92.14)	143/9 (n = 152) (94.08)	0.513

P values were obtained from two-sided comparisons of difference between the 14d-VA group and the 14d-VAC group. VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.

Table 6 Univariate analysis of factors related to eradication rates, n (%)

Variables	14d-EA group and 14d-B-quadruple group (n = 353)		14d-VA group and 14d-VAC group (n = 325)
	Eradication rate (success/total)	P value	Eradication rate (success/total)	P value
Gender
Male	151/158 (95.57)	0.879	141/149 (94.63)	0.902
Female	187/195 (95.90)		166/176 (94.32)
Age
≤ 60 years	319/333 (95.80)	0.591	278/295 (94.24)	0.892
> 60 years	19/20 (95.00)		29/30 (96.67)
Fixed occupation
Yes	209/219 (95.43)	0.706	184/194 (94.85)	0.713
No	129/134 (96.27)		123/131 (93.89)
BMI, kg/m²
< 22	116/123 (94.31)	0.271	128/136 (94.12)	0.092
22-25	140/147 (95.24)		116/119 (97.48)
> 25	82/83 (98.80)		63/70 (90.00)
BSA, m²
< 1.65	171/181 (94.48)	0.223	174/184 (94.57)	0.926
≥ 1.65	167/172 (97.09)		133/141 (94.33)
Education status
Primary	28/30 (93.33)	0.280	25/26 (96.15)	0.954
Junior high school	45/47 (95.74)		38/40 (95.00)
High school	54/58 (93.10)		58/61 (95.08)
College	154/161 (95.65)		140/148 (94.59)
Above university	57/57 (100.00)		46/50 (92.00)
Place of residence
Urban area	278/285 (97.54)	0.001a	252/263 (95.82)	0.004a
Suburban area	36/43 (83.72)		31/38 (81.58)
Rural area	24/25 (96.00)		24/24 (100.00)
Smoking
Yes	85/89 (95.51)	1.000	75/80 (93.75)	0.969
No	253/264 (95.83)		232/245 (94.69)
Drinking
Frequent	21/22 (95.45)	0.822	18/19 (94.74)	0.768
Occasional	89/92 (96.74)		81/87 (93.10)
None	228/239 (95.40)		208/219 (94.98)
Past medical history
Yes	59/61 (96.72)	0.949	53/55 (96.36)	0.724
No	279/292 (95.55)		254/270 (94.07)
Family infection of H. pylori
Yes	108/112 (96.43)	0.895	86/93 (92.47)	0.449
No	126/132 (95.45)		129/134 (96.27)
Undetected	104/109 (95.41)		92/98 (93.88)
Digestive symptoms
Yes	256/268 (95.52)	0.945	246/259 (94.98)	0.611
No	82/85 (96.47)		61/66 (92.42)
Endoscopy diagnosis
Yes	230/242 (95.04)	0.489	205/219 (93.61)	0.333
No	108/111 (97.30)		102/106 (96.23)
Atrophic gastritis
Yes	62/65 (95.38)	1.000	59/63 (93.65)	0.995
No	276/288 (95.83)		248/262 (94.66)
History of antibiotics use in 2 years
Yes	170/183 (92.90)	0.006a	150/165 (90.91)	0.004a
No	168/170 (98.82)		157/160 (98.13)
Relief of symptoms
No symptoms	82/85 (96.47)	0.418	61/66 (92.42)	0.318
Remission	173/184 (94.02)		161/168 (95.83)
Symptoms disappeared	69/70 (98.57)		71/75 (94.67)
No	14/14 (100.00)		14/16 (87.50)
Adverse events
Yes	21/21 (100.00)	1.000	31/33 (93.94)	1.000
No	317/332 (95.48)		276/292 (94.52)
Compliance
Good	337/350 (96.29)	0.005a	299/314 (95.22)	0.018a
Poor	1/3 (33.33)		8/11 (72.73)

^aP < 0.05.

BMI: Body mass index; BSA: Body surface area; EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth; VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.

Table 7 Multivariate analysis of factors related to eradication rates

Variables	14d-EA group and 14d-B-quadruple group (n = 353)			14d-VA group and 14d-VAC group (n = 325)
	OR	OR 95%CI	P value	OR	OR 95%CI	P value
History of antibiotics use in 2 years	7.242	[1.489, 35.214]	0.014a	5.643	[1.548, 20.572]	0.009a
Compliance	83.037	[3.805, 1812.024]	0.005a	9.381	[2.064, 42.633]	0.004a
Urban area	6.064	[1.938, 18.975]	0.002a	3.906	[1.357, 11.248]	0.012a

^aP < 0.05.

EA: Esomeprazole-amoxicillin; B-quadruple: Esomeprazole-amoxicillin-clarithromycin-bismuth; VA: Vonoprazan-amoxicillin; VAC: Vonoprazan-amoxicillin-clarithromycin.