A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure

Stealth BioTherapeutics Inc.46 sites in 10 countries308 target enrollmentOctober 20, 2016

ConditionsHeart Failure

Interventionselamipretide Placebo

Drugselamipretide Placebo

Overview

Phase: Phase 2
Intervention: elamipretide
Conditions: Heart Failure
Sponsor: Stealth BioTherapeutics Inc.
Enrollment: 308
Locations: 46
Primary Endpoint: Change in NT-proBNP between Baseline and Day 8/Early Discharge
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase 2 randomized, double-blind, placebo-controlled study to evaluate the cardiac and renal effects of short term treatment with elamipretide in patients hospitalized with congestion due to heart failure

Registry

clinicaltrials.gov

Start Date

October 20, 2016

End Date

November 27, 2017

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Stealth BioTherapeutics Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•A history of chronic heart failure for at least 1 month
•Treated with ≥40 mg/day of furosemide or bumetanide ≥1 mg/day or torasemide ≥10 mg/day for at least 1 month
•In-hospital observation/admission and treatment for ≤72 hours and primary cause for admission is heart failure with persistent congestion in the opinion of the Investigator (i.e. at least +2 pitting oedema and/or an estimated 8 kg gain in weight over baseline over the past 4 weeks) requiring intravenous loop diuretic therapy
•Sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours
•Systolic blood pressure \>90 mmHg and considered to be haemodynamically stable, in the opinion of the Investigator
•History of left ventricular ejection fraction (LVEF) ≤40% confirmed in the last 18 months
•NT-proBNP \>1500 pg/ml or BNP \>500 pg/ml
•An eGFR of \>30 mL/min/1.73 m2 using the eGFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American)

Exclusion Criteria

•Acute coronary syndrome, stroke, or transient ischemic attack (TIA), coronary or peripheral revascularization procedures, valve procedures, OR any major surgical procedure within the previous 6 weeks
•Invasive cardiac investigation and/or treatment (i.e. coronary angiography, percutaneous coronary intervention \[PCI\] or surgery) or other surgical procedure planned in the next 4 weeks
•Use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study
•Severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation
•Acute mechanical cause of decompensated heart failure such as papillary muscle rupture
•Obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis)
•Second or third degree heart block unless the subject has a ventricular pacemaker
•Atrial fibrillation/flutter with sustained ventricular response of \>130 bpm
•Placement of a ventricular resynchronization device within the previous 6 weeks
•Treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission

Arms & Interventions

20 mg elamipretide

20 mg elamipretide once daily for 7 consecutive days

Intervention: elamipretide

Placebo

Placebo once daily for 7 consecutive days

Intervention: Placebo

Outcomes

Primary Outcomes

Change in NT-proBNP between Baseline and Day 8/Early Discharge

Time Frame: Baseline to Day 8

Secondary Outcomes

The patient and physician global assessment is a 7-point scale which either the patient or the physician will assess from 0 to 10 and will be mathematically averaged on a daily basis in order to compare the different averages throughout the study.(Baseline to Day 3 and Day 8)
The average daily dose of diuretic (furosemide - adjusted for thiazide dose if administered) between baseline and Day 3 and Day 8/Early Discharge(Baseline to Day 3 and Day 8)
All adverse events, serious adverse events and SUSARs will be summarised per treatment group, namely elamipretide versus placebo, and compared at the end of the study.(Baseline to Day 8)
Half-life (T1/2)(Baseline to Day 8)
Area under the concentration - time curve from 0-24 h (AUC 0-24)(Baseline to Day 8)
Area under the concentration - time curve from 0- infinity (AUC 0-∞)(Baseline to Day 8)
Peak Plasma Concentration (Cmax)(Baseline to Day 8)
Number of patients staying in the same functional renal function class measured with MDRD formula compared to the number of patients with decreasing or increasing renal function measured with MDRD formula(Baseline to Day 3 and Day 8)
Number of patients showing a decrease in body weight compared to baseline as well as number of patients showing either no decrease or an increase in body weight compared to baseline(Baseline to Day 3 and Day 8)
Calculation of decrease or increase in body weight normalised to the average dose (in mg) of furosemide administered(Baseline to Day 3 and Day 8)