Antioxidant therapy in acute, chronic and post-endoscopic retrograde cholangiopancreatography pancreatitis: An updated systematic review and meta-analysis

Table 3 Controlled clinical trials for antioxidant management to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

Ref.	Drug/supplements	Study design	Jadad score	n	Treatment (intervention)		Outcome (results)		Adverse effects/events	Other comments
					Case	Control	Primary	Other
Abbasinazari et al[40], 2011	Allopurinol	Randomized double blind clinical trial	3	74	29 patients;	45 patients; no medication	Rate of PEP1(11.5% vs 12.5%)	Serum amylase activity1	-	-
Martinez-Torres et al[41], 2009	Allopurinol	Randomized; double-blind; placebo-controlled	5	170	85 patients; 300 mg oral allopurinol 15 h and 3 h before ERCP	85 patients; placebo	Rate of PEP ↓ (2.3% vs 9.4%)	Serum amylase activity ↓	-	21.7% absolute benefit in patients with high-risk procedures favoring allopurinol, no difference in low-risk procedures
Kapetanos et al[42], 2009	Pentoxifylline	Randomized;	2	590	205 patients; 400 mg oral Pentoxifylline, 40 h, 32 h, 24 h, 16 h and 8 h before ERCP (total dose 2 g)	205 patients; no medication	Rate of PEP1(7.3% vs 2.9%)	TNF-α1IL-61	-	-
	Octreotide				180 patients; 0.5 mg subcutaneous octreotide, 64 h, 56 h, 48 h, 40 h, 32 h, 24 h, 16 h and 8 h before ERCP (total dose 4 mg)	205 patients; no medication	Rate of PEP1(5% vs 2.9%)	TNF-α↓IL-61
Romagnuolo et al[43], 2008	Allopurinol	Randomized; double blind; placebo- controlled	4	586	293 patients; 300 mg oral allopurinol 60 min before ERCP	293 patients; placebo	Rate of PEP1(5.5% vs 4.1%)	Disease-related adverse events1Procedure-related complications1Hospitalization1	-	In the non–high-risk group (n = 520), the crude PEP rates were 5.4% for allopurinol and 1.5% for placebo (P = 0.017), favoring placebo, indicating harm associated with allopurinol, whereas in the high-risk group (n = 66), the PEP rates were 6.3% for allopurinol and 23.5% for placebo (P = 0.050), favoring allopurinol
Kapetanos et al[44], 2007	Pentoxifylline	Randomized;	2	320	158 patients; 400 mg oral pentoxifylline, 40 h, 32 h, 24 h, 16 h and 8 h before ERCP (total dose 2 g)	162 patients; no medication	Rate of PEP1(5.6% vs 3%)	Hemorrhage1Serum amylase activity1	Nausea and vomiting in 10% of the patients who received the drug	-
Milewski et al[45], 2006	N-acetylcysteine	Randomized; placebo-controlled	2	106	55 patients; 600 mg oral N-acetylcysteine 24 h and 12 h before ERCP and 1200 mg IV for 2 d after the ERCP	51 patients; isotonic IV saline b.d for 2 d after the ERCP	Rate of PEP1(7.3% vs 11.8%)	Urine amylase activity1Serum amylase activity1	-	-
Katsinelos et al[46], 2005	Allopurinol	Randomized; double blind; placebo-controlled	4	250	125 patients; 600 mg oral allopurinol 15 and 3 h before ERCP	118 patients; placebo	Rate of PEP ↓(3.2% vs 17.8%)	Hospitalization ↓Severity of Pancreatitis ↓	-	-
Katsinelos et al[47], 2005	N-acetylcysteine	Randomized; double-blind; placebo-controlled	3	256	124 patients; 70 mg/kg 2 h before and 35 mg/kg at 4 h intervals for a total of 24 h after the procedure	125 patients; placebo (normal saline solution)	Rate of PEP1Hospitalization1	-	Nausea Skin rash Diarrhea Vomiting	2 patients with suspected SOD
Mosler et al[48], 2005	Allopurinol	Randomized; double blind; placebo- controlled	4	701	355 patients; 600 mg 4 h and 300 mg 1 h oral allopurinol before ERCP	346 patients; placebo	Rate of PEP1(13.0% vs 12.1%)	Severity of pancreatitis1	-	4% absolute benefit in high-risk patients; 4% absolute harm in average risk
Lavy et al[49], 2004	Natural β-carotene	Randomized; double-blind; placebo-controlled	5	321	141 patients; 2 g oral β-carotene 12 h before ERCP	180 patients; placebo	Rate of PEP1(10% vs 9.4%)	Severe pancreatitis ↓	-	-
Budzyńska et al[50], 2001	Allopurinol	Randomized; placebo-controlled	3	300	99 patients; 200 mg oral Allopurinol 15 h and 3 h before ERCP	101 patients; placebo	Rate of PEP1(12.1% vs 7.9%)	Severity of pancreatitis1	-	3-arm study, with third arm (n = 100) given prednisone

¹No significant difference between groups. ↑: Significant increase as compared with control; ↓: Significant decrease as compared with control; PEP: Post-endoscopic pancreatitis.