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

Phase 2

Completed

• Conditions: Heart Failure
• Interventions: Drug: Placebo; Drug: elamipretide

• Registration Number: NCT02914665
• Lead Sponsor: Stealth BioTherapeutics Inc.

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-09-14
• Study First Submitted QC: 2016-09-22
• Study First Posted: 2016-09-26
• Study Start: 2016-10-20
• Primary Completion: 2017-11-27
• Study Completion: 2017-11-27
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-26
• Last Update Posted: 2020-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 308

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo once daily for 7 consecutive days
20 mg elamipretide	elamipretide	20 mg elamipretide once daily for 7 consecutive days

Primary Outcome Measures

Name	Time	Method
Change in NT-proBNP between Baseline and Day 8/Early Discharge	Baseline to Day 8

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (46)

Hospital Onze Lieve Vrouw campus Aalst; 🇧🇪 Aalst, Belgium

Hospital ZNA Middelheim; 🇧🇪 Antwerp, Belgium

Department of Internal Diseases, "Multiprofile Hospital for Active Treatment Sveta Ekaterina - Dimitrovgrad" EOOD; 🇧🇬 Dimitrovgrad, Bulgaria

Clinic of Cardiology, "Second Multiprofile Hospital for Active Treatement - Sofia" EAD; 🇧🇬 Sofia, Bulgaria

Clinic of Cardiology, Multiprofile Hospital for Active Treatment National Heart Hospital" EAD; 🇧🇬 Sofia, Bulgaria

Clinic of Cardiology, "City Clinic University Multiprofile Hospital for Active Treatment" EOOD; 🇧🇬 Sofia, Bulgaria

Clinic of Internal Diseases, "Multiprofile Hospital for Active Treatment, "Sveta Anna Sofia" AD; 🇧🇬 Sofia, Bulgaria

Department of Cardiology, "Multiprofile Regional Hospital for Active Treatement Dr. Stefan Cherkezov" AD; 🇧🇬 Veliko Tarnovo, Bulgaria

Hôpital Henri Mondor; 🇫🇷 Créteil, France

CHU de Rangueil; 🇫🇷 Toulouse Cedex 9, France

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