This multicenter multinational RCT designed to compare efficacy of suppository indomethacin and NAC for prevention of PEP.

During a 6 month period, all of the patients indicated for ERCP in 7 referral centers of 4 countries randomly assigned to receive either 1200 mg oral NAC (group A), indomethacin suppository 100mg (group B), 1200 mg oral NAC plus indomethacin suppository 100mg (group C) or placebo (group D) two hour before ERCP. The primary outcomes were the rate and severity of any PEP.

a total of 432 patients included (average age 57.3 y, 41.4% male). The participants were originally citizens of 6 countries (60.87% Caucasian). The patients were randomly allocated to receive either NAC (group A, 84 cases), rectal indomethacin (group B, 138 cases), NAC + rectal indomethacin (group C, 115 cases) or placebo (group D, 95 cases). The rate of bleeding and perforation after procedures was 3.94% and 2.54% respectively. The rate of PEP in groups A, B and C in comparison with D (placebo) were 10.7%, 17.4%, 7.8% vs. 20% (P = 0.08, 0.614 & 0.01 respectively). The NNT for NAC, indomethacin and NAC + indomethacin were 11, 38 and 8 respectively. 49.18% of the PEP cases were mild with average duration of hospital stay 4.5 days.

Oral NAC is more effective than rectal indomethacin when compared to placebo for prevention of PEP and the combination of NAC and Indomethacin had the lowest incidence of PEP and may have synergistic effect in preventing of PEP.