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

NCT02914665 | Completed Phase 2 DMC

• 2 other identifiers: SPIHF-2042016-000126-19
• Study Type: interventional
• Target: 308
• Locations: 10 countries
• Sites: 46

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

Conditions

Heart Failure

Keywords

Heart failure; diuresis; dropsy; congestion; elamipretide; MTP-131; Bendavia™

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Day 8

Secondary Outcomes (10)

• 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

• 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

Study Arms (2)

20 mg elamipretide

EXPERIMENTAL

20 mg elamipretide once daily for 7 consecutive days

Drug: elamipretide

Placebo

PLACEBO COMPARATOR

Placebo once daily for 7 consecutive days

Drug: Placebo

Interventions

elamipretide DRUG

20 mg elamipretide administered intravenously once daily for 7 consecutive days

Also known as: MTP-131, Bendavia

20 mg elamipretide

Placebo DRUG

Placebo administered intravenously once daily for 7 consecutive days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (46)

Hospital Onze Lieve Vrouw campus Aalst

Aalst, 9300, Belgium

Location

Hospital ZNA Middelheim

Antwerp, 2020, Belgium

Location

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

Dimitrovgrad, 6400, Bulgaria

Location

Clinic of Cardiology, "Second Multiprofile Hospital for Active Treatement - Sofia" EAD

Sofia, 1202, Bulgaria

Location

Clinic of Cardiology, Multiprofile Hospital for Active Treatment National Heart Hospital" EAD

Sofia, 1309, Bulgaria

Location

Clinic of Cardiology, "City Clinic University Multiprofile Hospital for Active Treatment" EOOD

Sofia, 1407, Bulgaria

Location

Clinic of Internal Diseases, "Multiprofile Hospital for Active Treatment, "Sveta Anna Sofia" AD

Sofia, 1750, Bulgaria

Location

Department of Cardiology, "Multiprofile Regional Hospital for Active Treatement Dr. Stefan Cherkezov" AD

Veliko Tarnovo, 5000, Bulgaria

Location

Hôpital Henri Mondor

Créteil, 94000, France

Location

CHU de Rangueil

Toulouse, 31059, France

Location

Hungarian Institute Of Cardiology, Department of Adult Cardiology

Budapest, 1096, Hungary

Location

Semmelweis University Heart and Vascular Center

Budapest, 1122, Hungary

Location

County St. George University Teaching Hospital, Department of Internal Medicine Cardiology

Székesfehérvár, 8000, Hungary

Location

Zala County Hospital Cardiology Department

Zalaegerszeg, 8900, Hungary

Location

Daugavpils Regional Hospital

Daugavpils, LV5417, Latvia

Location

Riga East Clinical University Hospital, Clinic Gailezers

Liepāja, LV1038, Latvia

Location

Liepaja Regional Hospital

Liepāja, LV3402, Latvia

Location

Pauls Stradins Clinical University Hospital, Latvian Centre of Cardiology

Riga, LV1002, Latvia

Location

Hospital Jeroen Bosch

's-Hertogenbosch, 5223 GV 's, Netherlands

Location

Deventer Hospital

Deventer, 7416 S, Netherlands

Location

Hospital Gelderse Vallei

Ede, 6716 RP, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Hospital Antonius/D&A research Genetic

Sneek, 8601 ZR, Netherlands

Location

Hospital Elisabeth -Tweesteden

Tilburg, 5042 AD, Netherlands

Location

Hospitals Gelre

Zutphen, 7207 AE, Netherlands

Location

Bieganski Provincial Specialist Hospital, Department of Cardiology, Clinic of Cardiology UM

Lodz, 91-347, Poland

Location

Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic Heart Failure and Transplantation

Warsaw, 04-628, Poland

Location

Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic of Coronary Heart Disease and Structural Heart Disease

Warsaw, 04-628, Poland

Location

Clinical Centre of Serbia, Emergency Centre

Belgrade, 11000, Serbia

Location

Clinical Centre of Serbia, Institute for Cardiovascular Diseases

Belgrade, 11000, Serbia

Location

Clinical Hospital Centre Bezanijska kosa

Belgrade, 11070, Serbia

Location

Clinical Hospital Centre Zemun

Belgrade, 11080, Serbia

Location

Institute for Cardiovascular Diseases of Vojvodina

Kamenitz, 21204, Serbia

Location

Clinical Centre Nis

Niš, 18000, Serbia

Location

Complexo Hospitalario Universitario de A Coruña

A Coruña, 15006 A, Spain

Location

Hospital Universitario de Bellvitge

Barcelona, 08907, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222 Majadahonda, Spain

Location

Hospital Alvaro Cunqueiro

Pontevedra, 36312 Vigo, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Consorci Hospital General Universitari de Valencia

Valencia, 46014, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Bradford Royal Infirmary

Bradford, BD6 6RJ, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure; Edema

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 26, 2016
• Study Start: October 20, 2016
• Primary Completion: November 27, 2017
• Study Completion: November 27, 2017
• Last Updated: July 28, 2020

Record last verified: 2020-07

Locations

SE (6); HU (4); BE (2); ES (9); LA (4); BU (6); PL (3); GB (3); FR (2); NL (7)