A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency

Background: Modern pancreatin preparations consist of enteric-coated micros pheres to protect the enzymes from gastric acid. There are, however, no cli nical trials comparing different sizes of pancreatin microspheres with rega rd to fat excretion and fat intake. Aim: To prove both equivalent efficacy and safety of conventional pancreati n microspheres and smaller pancreatin minimicrospheres in patients with exo crine insufficiency due to chronic pancreatitis. Methods: In this prospective, randomized, double-blind, multicentre, crosso ver trial, patients with a stool fat excretion of > 7.5 g/day during a plac ebo period were randomly assigned either to the minimicrosphere/ microspher e treatment sequence or vice versa, The primary end-point was the coefficie nt of fat absorption, which was calculated from fat excretion and fat intak e during the course of a standardized diet. Stool weight, clinical symptoms and the safety of the preparations were also evaluated. Results: Thirty-seven patients entered the study, of whom 23 fulfilled the criteria for the crossover period, In the per protocol analysis (n = 18), t he 90% confidence intervals for the coefficient of fat absorption of both c rossover periods lay entirely within the equivalence range (P = 0.02). The intention-to-treat analysis revealed similar results, but the equivalence r ange was slightly missed (P = 0.07). Similar results were obtained for the secondary parameters and the reported adverse events. Conclusions: Pancreatin minimicrospheres have been shown to be equally effe ctive as microspheres in improving the coefficient of fat absorption in pat ients with exocrine insufficiency due to chronic pancreatitis.