- Design
- 24-week double-blind, parallel-group, placebo-controlled randomised trial at two academic centres
- Population
- 107 adults aged 18-60 with chronic pancreatitis by Mayo Clinic criteria and chronic abdominal pain; mean age 34.4 years, 71% men, 66% idiopathic
- Primary outcome
- between-group difference in change in Izbicki pain score from baseline to 12 weeks
- Effect
- -2.5 (95% CI -9.3 to 4.2; p = 0.49); similar at 24 weeks; adverse events mild and comparable
A 24-week double-blind, placebo-controlled trial at two Indian academic centres randomised 107 adults aged 18 to 60 with chronic pancreatitis by Mayo Clinic criteria and chronic abdominal pain to non-enteric-coated pancreatic enzyme replacement or placebo for 12 weeks. Mean age was 34.4 years, 71% were men and 66% had idiopathic disease — a population that will look familiar to anyone running a pancreas clinic in India and quite unlike the alcohol-dominated Western series.
The primary outcome, change in Izbicki pain score at 12 weeks, showed no between-group difference. Results at 24 weeks, included specifically to look for carry-over effects, were the same. Adverse events were mild and comparable.
The rationale being tested was specific and physiological: non-enteric-coated preparations release protease in the duodenum, which should suppress cholecystokinin release and reduce pancreatic stimulation. It is a coherent mechanism, it is why the non-enteric-coated formulation was chosen, and it did not translate into pain relief.
What this changes is the framing of a common prescription. Enzyme replacement in chronic pancreatitis remains indicated for exocrine insufficiency — steatorrhoea, weight loss, nutritional deficiency — and there is no case for prescribing it, or continuing it, on the expectation of analgesia.
- Prescribe pancreatic enzymes for exocrine insufficiency, not for pain
- Where a patient is already on enzymes for pain alone, review whether there is a nutritional indication before continuing
- Address pain through the established routes — analgesic ladder, ductal assessment, smoking and alcohol cessation, and neuropathic agents where appropriate
- Set expectations at the point of prescribing; a patient told enzymes will help the pain will attribute failure to the dose
- Note the population: young adults with largely idiopathic disease, which is the Indian phenotype rather than the Western one
The statistics, in plain English
The between-group difference in Izbicki score was -2.5 with a 95% confidence interval of -9.3 to 4.2 — an interval straddling zero on a scale where this width is modest, so this is a reasonably informative null rather than an underpowered one at 107 patients. One secondary outcome, painful days at 12 weeks, reached significance in isolation (p = 0.02). With a null primary outcome and multiple secondary outcomes tested, a single significant secondary result is what chance produces, and the authors' own conclusion does not rest on it.
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