Impact of non-enteric-coated pancreatic enzyme replacement therapy (NEPERT) on pain in patients with chronic pancreatitis: a double-blind, parallel-group, placebo-controlled, randomised trial.

BACKGROUND: Pain in chronic pancreatitis (CP) is multifactorial. Efficacy of pancreatic enzyme replacement therapy (PERT) for pain remains uncertain. OBJECTIVE: To assess the effect of non-enteric-coated PERT (NEPERT) on pain in CP. DESIGN: In this 24-week, double-blind, placebo-controlled, randomised trial, we enrolled adults aged 18-60 years with CP (Mayo Clinic criteria) and chronic abdominal pain at two academic centres. Participants were randomised to NEPERT (protease 30 000U, lipase 25 000U, amylase 8000U per capsule) or placebo for 12 weeks. Outcomes were measured at 12 and 24 weeks. Primary outcome was between-group differences in change in Izbicki pain score from baseline to 12 weeks. Secondary outcomes were Izbicki and Visual Analogue Scale (for pain) at 24 weeks, painful days, analgesic/hospitalisation requirements, patient's global impression of change and quality of life at 12 and 24 weeks. The reason for secondary outcomes assessment at 24 weeks was to evaluate carry-over effects after NEPERT. Primary analysis used repeated-measures mixed-effects models. RESULTS: 107 patients (mean (SD) age 34.4 (11.4) years; 71% men; 66% idiopathic) were randomised (53 placebo; 54 NEPERT). On intention-to-treat analysis, there were no significant between-group differences in pain improvement at 12 weeks (Izbicki -2.5 (95% CI -9.3 to 4.2), p=0.49). Findings were similar at 24 weeks. Secondary outcomes were also similar at 12 and 24 weeks, except for a higher proportion of participants reporting painful days at 12 weeks in the NEPERT group (mean group differences (95% CI) of -14.5 (-26.0 to -3.0); p=0.02). Adverse events were mild, self-limiting and comparable between groups. CONCLUSIONS: In adults with painful CP, NEPERT did not improve pain compared with placebo. TRIAL REGISTRATION NUMBER: NCT05042284.