Propionyl-l-carnitine in intermittent claudication: Double-blind, placebo-controlled, dose titration, multicenter study

Objectives. The aim of this double-blind, placebo-controlled, dose titration, multicenter trial was to assess the efficacy and safety of propionyl-l-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 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 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 dose of 1 to 2 g/day, appears to be effective and well tolerated, with minimal adverse effects.