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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02914665
• Other study ID #: SPIHF-204
• Secondary ID: 2016-000126-19
• Status: Completed
• Phase: Phase 2
• Start date: October 20, 2016
• Est. completion date: November 27, 2017

Study information

• Verified date: July 2020
• Source: Stealth BioTherapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 308
• Est. completion date: November 27, 2017
• Est. primary completion date: November 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• elamipretide
20 mg elamipretide administered intravenously once daily for 7 consecutive days
• Placebo
Placebo administered intravenously once daily for 7 consecutive days

Locations

Country	Name	City	State
Belgium	Hospital Onze Lieve Vrouw campus Aalst	Aalst
Belgium	Hospital ZNA Middelheim	Antwerp
Bulgaria	Department of Internal Diseases, "Multiprofile Hospital for Active Treatment Sveta Ekaterina - Dimitrovgrad" EOOD	Dimitrovgrad
Bulgaria	Clinic of Cardiology, "City Clinic University Multiprofile Hospital for Active Treatment" EOOD	Sofia
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 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
France	Hôpital Henri Mondor	Créteil
France	CHU de Rangueil	Toulouse Cedex 9
Hungary	Hungarian Institute Of Cardiology, Department of Adult Cardiology	Budapest
Hungary	Semmelweis University Heart and Vascular Center	Budapest
Hungary	County St. George University Teaching Hospital, Department of Internal Medicine Cardiology	Székesfehérvár
Hungary	Zala County Hospital Cardiology Department	Zalaegerszeg
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	Riga East Clinical University Hospital, Clinic Gailezers	Liepaja
Latvia	Pauls Stradins Clinical University Hospital, Latvian Centre of Cardiology	Riga
Netherlands	Deventer Hospital	Deventer
Netherlands	Hospital Gelderse Vallei	Ede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Hospital Jeroen Bosch	Hertogenbosch
Netherlands	Hospital Antonius/D&A research Genetic	Sneek
Netherlands	Hospital Elisabeth -Tweesteden	Tilburg
Netherlands	Hospitals Gelre	Zutphen
Poland	Bieganski Provincial Specialist Hospital, Department of Cardiology, Clinic of Cardiology UM	Lodz
Poland	Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic Heart Failure and Transplantation	Warsaw
Poland	Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic of Coronary Heart Disease and Structural Heart Disease	Warsaw
Serbia	Clinical Centre of Serbia, Emergency Centre	Belgrade
Serbia	Clinical Centre of Serbia, Institute for Cardiovascular Diseases	Belgrade
Serbia	Clinical Hospital Centre Bezanijska kosa	Belgrade
Serbia	Clinical Hospital Centre Zemun	Belgrade
Serbia	Clinical Centre Nis	Nis
Serbia	Institute for Cardiovascular Diseases of Vojvodina	Sremska Kamenica
Spain	Hospital Universitario de Bellvitge	Barcelona
Spain	Complexo Hospitalario Universitario de A Coruña	Coruña
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Alvaro Cunqueiro	Pontevedra
Spain	Consorci Hospital General Universitari de Valencia	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Torbay Hospital	Torquay

Sponsors (1)

Lead Sponsor	Collaborator
Stealth BioTherapeutics Inc.

Countries where clinical trial is conducted

Belgium,  Bulgaria,  France,  Hungary,  Latvia,  Netherlands,  Poland,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in NT-proBNP between Baseline and Day 8/Early Discharge		Baseline to Day 8
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Half-life (T1/2)		Baseline to Day 8
Secondary	Area under the concentration - time curve from 0-24 h (AUC 0-24)		Baseline to Day 8
Secondary	Area under the concentration - time curve from 0- infinity (AUC 0-8)		Baseline to Day 8
Secondary	Peak Plasma Concentration (Cmax)		Baseline to Day 8