Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study

J Am Coll Cardiol. 1995 Nov 15;26(6):1411-6. doi: 10.1016/0735-1097(95)00344-4.


Objectives: The aim of this double-blind, placebo-controlled, dose titration, multicenter trial was to assess the efficacy and safety of propionyl-carnitine in intermittent claudication.

Background: Human and animal studies indicate that propionyl-L-carnitine increases carnitine content and improves energy metabolism in the ischemic skeletal muscle.

Methods: After a 2-week preliminary period to assess maximal walking distance, 245 patients were randomly assigned to receive propionyl-L-carnitine (n = 118) or placebo (n = 127). The initial oral dose of 500 mg twice daily was increased at 2-month intervals to 2 g/day and then to 3 g/day in patients showing improvement in treadmill performance < 30% over baseline. Efficacy analysis was conducted for the 214 patients who completed the 24 weeks of treatment by comparing the effect of placebo and propionyl-L-carnitine on day 180.

Results: Analysis of variance showed a significant improvement of 73 +/- 9% (mean +/- SE) in maximal walking distance with propionyl-L-carnitine (n = 99) compared with 46 +/- 6% for placebo (n = 115, p = 0.03). For distance walked at onset of claudication, propionyl-L-carnitine showed about double the improvement of placebo; however, the difference was not statistically significant. There were no changes in electrocardiographic and routine biochemical and hematologic tests that would indicate an adverse effect of propionyl-L-carnitine. Adverse events requiring drug discontinuation (11 in the propionyl-L-carnitine group, 3 in the placebo group) were unrelated to study medication. The dose titration design of the study also provided information on the dose-response relation. Slightly less than 67% of patients were expected to improve their maximal walking distance by at least 30%, assuming 2 g/day of propionyl-L-carnitine (95% confidence interval 0.51 to 0.70). The response rate during the entire titration course was significantly in favor of propionyl-L-carnitine compared with placebo.

Conclusions: Although the precise mode of therapeutic action requires clarification, propionyl-L-carnitine, at a dose of 1 to 2 g/day, appears to be effective and well tolerated, with minimal adverse effects.

Publication types

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

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Cardiotonic Agents / administration & dosage*
  • Cardiotonic Agents / adverse effects
  • Carnitine / administration & dosage
  • Carnitine / adverse effects
  • Carnitine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Intermittent Claudication / drug therapy*
  • Male
  • Middle Aged
  • Treatment Outcome


  • Cardiotonic Agents
  • propionylcarnitine
  • Carnitine