Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.

ABSTRACT

BACKGROUND AND AIM: The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS: In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2 months followed by open-label antioxidants for the next 4 months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS: We randomized 42 and 45 patients (mean age 29.3 years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2 months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P = 0.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P = 0.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P = 0.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P = 0.01). Needed-to-treat was 4.8. Pain reduction persisted at 6 months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P = 0.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION: Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic naïve patients with chronic calcific pancreatitis.