Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide

BACKGROUND: Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction.METHODS AND RESULTS: In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kgCONCLUSIONS: This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464.