Clinical trial NCT02914665: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Heart failure
diuresis
dropsy
congestion
elamipretide
MTP-131
Bendavia™
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-26
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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
* 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

Primary outcomes:
measure: Change in NT-proBNP between Baseline and Day 8/Early Discharge
timeFrame: Baseline to Day 8
Secondary outcomes:
measure: 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
timeFrame: Baseline to Day 3 and Day 8
measure: 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
timeFrame: Baseline to Day 3 and Day 8
measure: Calculation of decrease or increase in body weight normalised to the average dose (in mg) of furosemide administered
timeFrame: Baseline to Day 3 and Day 8
measure: 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.
timeFrame: Baseline to Day 3 and Day 8
measure: The average daily dose of diuretic (furosemide - adjusted for thiazide dose if administered) between baseline and Day 3 and Day 8/Early Discharge
timeFrame: Baseline to Day 3 and Day 8
measure: 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.
timeFrame: Baseline to Day 8
measure: Half-life (T1/2)
timeFrame: Baseline to Day 8
measure: Area under the concentration - time curve from 0-24 h (AUC 0-24)
timeFrame: Baseline to Day 8
measure: Area under the concentration - time curve from 0- infinity (AUC 0-∞)
timeFrame: Baseline to Day 8
measure: Peak Plasma Concentration (Cmax)
timeFrame: Baseline to Day 8
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Hospital Onze Lieve Vrouw campus Aalst
city: Antwerp
country: Belgium
facility: Hospital ZNA Middelheim
city: Dimitrovgrad
country: Bulgaria
facility: Department of Internal Diseases, "Multiprofile Hospital for Active Treatment Sveta Ekaterina - Dimitrovgrad" EOOD
city: Sofia
country: Bulgaria
facility: Clinic of Cardiology, "Second Multiprofile Hospital for Active Treatement - Sofia" EAD
city: Sofia
country: Bulgaria
facility: Clinic of Cardiology, Multiprofile Hospital for Active Treatment National Heart Hospital" EAD
city: Sofia
country: Bulgaria
facility: Clinic of Cardiology, "City Clinic University Multiprofile Hospital for Active Treatment" EOOD
city: Sofia
country: Bulgaria
facility: Clinic of Internal Diseases, "Multiprofile Hospital for Active Treatment, "Sveta Anna Sofia" AD
city: Veliko Tarnovo
country: Bulgaria
facility: Department of Cardiology, "Multiprofile Regional Hospital for Active Treatement Dr. Stefan Cherkezov" AD
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Toulouse Cedex 9
country: France
facility: CHU de Rangueil
city: Budapest
country: Hungary
facility: Hungarian Institute Of Cardiology, Department of Adult Cardiology
city: Budapest
country: Hungary
facility: Semmelweis University Heart and Vascular Center
city: Székesfehérvár
country: Hungary
facility: County St. George University Teaching Hospital, Department of Internal Medicine Cardiology
city: Zalaegerszeg
country: Hungary
facility: Zala County Hospital Cardiology Department
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Liepaja
country: Latvia
facility: Riga East Clinical University Hospital, Clinic Gailezers
city: Liepaja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital, Latvian Centre of Cardiology
city: Deventer
country: Netherlands
facility: Deventer Hospital
city: Ede
country: Netherlands
facility: Hospital Gelderse Vallei
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Hertogenbosch
country: Netherlands
facility: Hospital Jeroen Bosch
city: Sneek
country: Netherlands
facility: Hospital Antonius/D&A research Genetic
city: Tilburg
country: Netherlands
facility: Hospital Elisabeth -Tweesteden
city: Zutphen
country: Netherlands
facility: Hospitals Gelre
city: Lodz
country: Poland
facility: Bieganski Provincial Specialist Hospital, Department of Cardiology, Clinic of Cardiology UM
city: Warsaw
country: Poland
facility: Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic Heart Failure and Transplantation
city: Warsaw
country: Poland
facility: Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic of Coronary Heart Disease and Structural Heart Disease
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Emergency Centre
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Institute for Cardiovascular Diseases
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Bezanijska kosa
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Zemun
city: Nis
country: Serbia
facility: Clinical Centre Nis
city: Sremska Kamenica
country: Serbia
facility: Institute for Cardiovascular Diseases of Vojvodina
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Coruña
country: Spain
facility: Complexo Hospitalario Universitario de A Coruña
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Pontevedra
country: Spain
facility: Hospital Alvaro Cunqueiro
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Consorci Hospital General Universitari de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital
Study officials:
References: