High-dose elamipretide significantly decreased left ventricular end-diastolic volume (-18 mL; P=0.009) and end-systolic volume (-14 mL; P=0.005) compared with placebo.
RCT (n=36)
Double-blind
randomized
Does a single infusion of elamipretide improve cardiac structure and function and is it safe in patients with heart failure with reduced ejection fraction?
A single infusion of the novel mitochondria-targeting peptide elamipretide is safe and acutely reduces left ventricular volumes in patients with HFrEF.
Mean Difference: -18
p-value: p=0.009 for LVEDV, 0.005 for LVESV
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·kg −1 ·h −1 ) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (−18 mL; P =0.009) and end-systolic volume (−14 mL; P =0.005) occurred at end infusion in the highest dose cohort. Conclusions 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.
Daubert et al. (2017) conducted an RCT in Heart failure with reduced ejection fraction (n=36). Elamipretide vs. Placebo was evaluated on Left ventricular end-diastolic volume and end-systolic volume (MD -18 mL for LVEDV, -14 mL for LVESV, p=0.009 for LVEDV, 0.005 for LVESV). High-dose elamipretide significantly decreased left ventricular end-diastolic volume (-18 mL; P=0.009) and end-systolic volume (-14 mL; P=0.005) compared with placebo.