A Phase 2 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

Status and phase

Completed

Phase 2

Conditions

Heart Failure

Treatments

Drug: Placebo

Drug: elamipretide

Study type

Interventional

Funder types

Industry

Identifiers

NCT02914665

SPIHF-204

2016-000126-19 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

308 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
Receipt of intravenous vasodilator therapy ≤ 6 hours prior to randomization
The presence of any mechanical assist device or listed for or a history of a heart transplant
Severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation)
Anuric in the previous 24 hours
Haemoglobin <9 g/dL at screening or planned blood transfusions in the next 30 days
Serum potassium >5.5 mEq/L
Marked proteinuria suggestive of nephrotic syndrome
Estimated GFR (eGFR) as per MDRD equation <30 ml/min
Serum albumin of < 2.8 g/dL
Liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >5 times the upper limit of normal (ULN)
Total bilirubin >2.0 times ULN in the absence of Gilbert's Syndrome
Current or planned ultrafiltration, paracentesis, haemofiltration or dialysis