AGGRESSIVE HYDRATION VERSUS HIGH-DOSE RECTAL INDOMETHACIN IN THE PREVENTION OF POST-ENDOSCOPIC RETROGRADE CHOLANGIO-PANCREATOGRAPHIC PANCREATITIS (AHRI-PEP)

Aims To compare vigorous peri-procedural hydration (vHR) with Lactated Ringer’s solution Ringer Lactate (LR) versus post-procedure rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs; Indomethacin 100mg).

Methods A prospective, randomized, open-label, non-inferiority, parallel-assigned, equal-allocation, controlled clinical trial (ClinicalTrials.govID:NCT03629600). Assuming PEP of 9% in the Indomethacin arm and non-inferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5% (nMaster Biostatistics2, CMC, Vellore, India). Consecutive adults referred for ERCP, satisfying pre-defined inclusion criteria, were enrolled from October, 2017 to February, 2018. Patients recruited to vHR received intravenous LR (COMPOUND SODIUM LACTATE INJECTION I.P., Inven Pharmaceutical, MP,India) @3mLkg^-1hr^-1 during the procedure, with 20cc/kg bolus immediately afterward, and then @3 mLkg^-1hr^-1 for another eight hours. Patients randomized to rectal Indomethacin received a per-rectal suppository (Indomethacin Suppository 100MgB.P., Galen Pharmaceutical, Gujrat,INDIA) immediately after completion of ERCP. The primary outcome was incidence of post-ERCP Pancreatitis (PEP) as defined by Cotton’s criteria. Secondary outcomes were: 1) incidence of post-ERCP pain; 2) Severity of PEP; 3) Clinical volume overload; 4) incidence and severity of other post-ERCP complications; and 7) death within seven days. Fisher´s exact test and Student t test were calculated.

Results 352/521 patients were randomized, 178 patients received vHR and 174 patients per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between two groups. Precutting was done in 104(29.5%), inadvertent PD-cannulation in 58(16.5%), mechanical lithotrypsy in 11(3.1%). None lost to follow-up. PEP occurred in 6(1.7%) overall, with 1(0.6%) in hydration arm and 5(2.9%) in indomethacin arm (p=0.094); absolute risk reduction 2.3%(95%CI: -0.3%to5%). Three patients developed severe PEP, all in the indomethacin arm. There was no statistically significant difference in between the two groups regarding the secondary outcomes.

Conclusions Vigorous peri-procedural hydration LR is non-inferior to post-procedure rectal Indomethacin for prevention of PEP.