PROPIONYL-L-CARNITINE IN INTERMITTENT CLAUDICATION - DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE TITRATION, MULTICENTER STUDY

Objectives. The aim of this double-blind, placebo-controlled, dose tit ration, multicenter trial was to assess the efficacy and safety of pro pionyl-L-carnitine in intermittent claudication. Background. Human and animal studies indicate that propionyl-L-carnitine increases carnitin e content and improves energy metabolism in the ischemic skeletal musc le. Methods. After a 2-week preliminary period to assess maximal walki ng distance, 245 patients were randomly assigned to receive propionyl- L-carnitine (n = 118) or placebo (n = 127). The initial oral dose of 5 00 mg twice daily was increased at 2-month intervals to 2 g/day and th en to 3 g/day in patients showing improvement in treadmill performance <30% over baseline. Efficacy analysis was conducted for the 214 patie nts who completed the 24 weeks of treatment by comparing the effect of placebo and propionyl-L-carnitine on day 180. Results. Analysis of va riance 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 effe ct of propionyl-L-carnitine. Adverse events requiring drug discontinua tion (II in the propionyl-L-carnitine group, 3 in the placebo group) w ere unrelated to study medication. The dose titration design of the st udy also provided information on the dose-response relation. Slightly less than 67% of patients were expected to improve their maximal walki ng 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-carn itine 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, wi th minimal adverse effects.