Author + information
- Received October 25, 1994
- Revision received June 9, 1995
- Accepted June 19, 1995
- Published online November 15, 1995.
- Gregorio Brevetti, MDa,*,
- Sergio Perna, MDa,
- Carlo Sabbá, MDa,*,
- Vincenzo Domenico Martone, MDa and
- Mario Condorelli, MDa
- ↵*Address for correspondence:Dr. Gregorio Brevetti, Via G. Iannelli 45/A, 80131 Napoli, Italy.
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 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.
This study was supported in part by a grant from Sigma-Tau SpA, Pomezia, Rome, Italy. Sigma-Tau SpA also supplied the placebo and active drug tablets.
- Received October 25, 1994.
- Revision received June 9, 1995.
- Accepted June 19, 1995.
- American College of Cardiology