AIMS: In patients with chronic heart failure, fatigue is independent of haemodynamic and neuroendocrine changes and possibly may be due to impaired muscle metabolism. Propionyl-L-carnitine, a carnitine derivative, was shown in previous studies to improve muscle metabolism. The objective of this study was to evaluate the effect of propionyl-L-carnitine on exercise capacity in mild moderate chronic heart failure patients, treated with ACE inhibitors and diuretics. METHODS AND RESULTS: This was a phase III, double-blind, randomized, parallel, multicentre study. The primary objective was the evaluation of the effect of propionyl-L-carnitine vs placebo on maximum exercise duration using a bicycle exercise test. The primary analysis performed in the intention-to-treat population (271 and 266 patients in propionyl-L-carnitine and placebo), showed no statistically significant difference between treatments. A difference of 15 s in favour of propionyl-L-carnitine was observed in the completer/complier population (P=0.092). An a priori specified subgroup analysis on patients stratified by baseline maximum exercise duration showed a trend of improvement in propionyl-L-carnitine patients with shorter maximum exercise duration. A non a priori specified analysis in patients stratified by ejection fraction (< or = 30% vs 30-40%), showed a statistically significant difference in maximum exercise duration in favour of propionyl-L-carnitine in those patients with a higher ejection fraction (40 s, P<0.01). There were no safety issues. CONCLUSION: The study fails to meet the primary objective, but confirms the good safety profile of propionyl-L-carnitine. An exploratory non-prespecified analysis suggests that propionyl-L-carnitine improves exercise capacity in patients with preserved cardiac function. This hypothesis needs to be confirmed by a specific tailored study.
RCT Entities:
AIMS: In patients with chronic heart failure, fatigue is independent of haemodynamic and neuroendocrine changes and possibly may be due to impaired muscle metabolism. Propionyl-L-carnitine, a carnitine derivative, was shown in previous studies to improve muscle metabolism. The objective of this study was to evaluate the effect of propionyl-L-carnitine on exercise capacity in mild moderate chronic heart failurepatients, treated with ACE inhibitors and diuretics. METHODS AND RESULTS: This was a phase III, double-blind, randomized, parallel, multicentre study. The primary objective was the evaluation of the effect of propionyl-L-carnitine vs placebo on maximum exercise duration using a bicycle exercise test. The primary analysis performed in the intention-to-treat population (271 and 266 patients in propionyl-L-carnitine and placebo), showed no statistically significant difference between treatments. A difference of 15 s in favour of propionyl-L-carnitine was observed in the completer/complier population (P=0.092). An a priori specified subgroup analysis on patients stratified by baseline maximum exercise duration showed a trend of improvement in propionyl-L-carnitinepatients with shorter maximum exercise duration. A non a priori specified analysis in patients stratified by ejection fraction (< or = 30% vs 30-40%), showed a statistically significant difference in maximum exercise duration in favour of propionyl-L-carnitine in those patients with a higher ejection fraction (40 s, P<0.01). There were no safety issues. CONCLUSION: The study fails to meet the primary objective, but confirms the good safety profile of propionyl-L-carnitine. An exploratory non-prespecified analysis suggests that propionyl-L-carnitine improves exercise capacity in patients with preserved cardiac function. This hypothesis needs to be confirmed by a specific tailored study.
Authors: Carmen Mingorance; Rosalía Rodríguez-Rodríguez; María Luisa Justo; María Alvarez de Sotomayor; María Dolores Herrera Journal: Vasc Health Risk Manag Date: 2011-03-28
Authors: Anna V Mathew; E Mitchell Seymour; Jaeman Byun; Subramaniam Pennathur; Scott L Hummel Journal: J Card Fail Date: 2015-10-20 Impact factor: 5.712