l-Carnitine plus cilostazol versus cilostazol alone for the treatment of claudication in patients with peripheral artery disease: A multicenter, randomized, double-blind, placebo-controlled trial

Intermittent claudication (IC) is the predominant symptom of peripheral artery disease (PAD), and is associated with reduced exercise capacity. The pathophysiology of IC is related to reduced blood flow and impaired skeletal muscle oxidative metabolism; however, the efficacy of metabolic therapies is not well established. We evaluated the effect of cilostazol plus l-carnitine versus cilostazol alone on exercise performance, quality of life (QOL), and safety. In a double-blind, placebo-controlled trial, PAD patients with stable IC were randomized to either l-carnitine 1 g or matching placebo twice-daily, on a background of cilostazol. Treadmill and QOL assessments were performed at baseline, 90, and 180 days. The primary endpoint was the difference between groups in the natural-log-transformed ( ln) ratio in peak walking time (PWT) between baseline and 180 days. The combination of cilostazol and l-carnitine was well tolerated. In the modified intent-to-treat population ( n = 145), the mean ln ratio in PWT was 0.241 for cilostazol/l-carnitine versus 0.134 for cilostazol/placebo ( p = 0.076), corresponding to mean increases of 1.99 and 1.36 minutes, respectively. In the per-protocol population ( n = 120), the mean ln ratio in PWT was 0.267 for cilostazol/l-carnitine versus 0.145 for cilostazol/placebo ( p = 0.048). QOL measures were also improved in the cilostazol/l-carnitine group. These findings support larger trials of l-carnitine in combination with cilostazol in the treatment of IC. ClinicalTrials.gov Identifier: NCT00822172