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

Aliment Pharmacol Ther. 1999 Jul;13(7):951-7. doi: 10.1046/j.1365-2036.1999.00566.x.


Background: Modern pancreatin preparations consist of enteric-coated microspheres to protect the enzymes from gastric acid. There are, however, no clinical trials comparing different sizes of pancreatin microspheres with regard to fat excretion and fat intake.

Aim: To prove both equivalent efficacy and safety of conventional pancreatin microspheres and smaller pancreatin minimicrospheres in patients with exocrine insufficiency due to chronic pancreatitis.

Methods: In this prospective, randomized, double-blind, multicentre, crossover trial, patients with a stool fat excretion of > 7.5 g/day during a placebo period were randomly assigned either to the minimicrosphere/microsphere treatment sequence or vice versa. The primary end-point was the coefficient of fat absorption, which was calculated from fat excretion and fat intake 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), the 90% confidence intervals for the coefficient of fat absorption of both crossover periods lay entirely within the equivalence range (P=0.02). The intention-to-treat analysis revealed similar results, but the equivalence range 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 effective as microspheres in improving the coefficient of fat absorption in patients with exocrine insufficiency due to chronic pancreatitis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chemistry, Pharmaceutical
  • Chronic Disease
  • Cross-Over Studies
  • Dietary Fats / metabolism*
  • Double-Blind Method
  • Exocrine Pancreatic Insufficiency / drug therapy*
  • Exocrine Pancreatic Insufficiency / metabolism
  • Feces
  • Female
  • Gastrointestinal Agents / administration & dosage*
  • Germany
  • Humans
  • Male
  • Microspheres
  • Middle Aged
  • Pancreatin / administration & dosage*
  • Pancreatitis / drug therapy*
  • Pancreatitis / metabolism
  • Particle Size
  • Prospective Studies


  • Dietary Fats
  • Gastrointestinal Agents
  • Pancreatin