Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study.
OBJECTIVE
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.
Brevetti
G
G
Department of Medicine, University Federico II, Naples, Italy.
Perna
S
S
Sabbá
C
C
Martone
V D
VD
Condorelli
M
M
D000284:Administration, Oral; D000704:Analysis of Variance; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002331:Carnitine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D002331:Carnitine