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
- Congestion due to heart failure10019280
- Registration Number
- NL-OMON45920
- Lead Sponsor
- Stealth BioTherapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 40
1. Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures
2. Aged *18 years
3. A history of chronic heart failure for at least 1 month
4. Treated with *40 mg/day of furosemide or bumetanide *1 mg/day or torasemide *10 mg/day for at least 1 month
5. 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
6. Able to be weighed
7. Sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours
Note: dose should be modified if dictated by the clinical situation and should be adjusted to the patient*s needs
8. Systolic blood pressure >/<=90 mmHg and considered to be haemodynamically stable, in the opinion of the Investigator
9. History of left ventricular ejection fraction (LVEF) *40% confirmed in the last 18 months
10. NT-proBNP >1500 pg/ml or BNP >500 pg/ml
11. An eGFR of >/<=30 mL/min/1.73 m2 using the MDRD study equation:
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)
12. Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study drug:
a. Abstinence, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use an acceptable method of contraception should they become sexually active
b. Maintenance of a relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis)
c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system
Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit)
13. Willing to adhere to the study requirements for the length of the trial
1. Completely bedridden for >2 weeks prior to admission. Patients should at least have been able to go the toilet and back and to get out of bed for meals at some time during this period
2. Known intolerance of furosemide
3. 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
4. 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
5. Use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study
6. Severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation
7. Acute mechanical cause of decompensated heart failure such as papillary muscle rupture
8. Obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis)
9. Second or third degree heart block unless the subject has a ventricular pacemaker
10. Atrial fibrillation/flutter with sustained ventricular response of >130 bpm
11. Placement of a ventricular resynchronization device within the previous 6 weeks
12. Treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission
13. Receipt of intravenous vasodilator therapy * 6 hours prior to randomization
14. The presence of any mechanical assist device or listed for or a history of a heart transplant
15. Suspected systemic infection or pneumonia and/or the need for antibiotic treatment between admission and time of consent. Patients given antibiotics without clear justification can be included as long as it is appropriate to discontinue the antibiotics
16. Severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation)
17. Anuric in the previous 24 hours
18. Haemoglobin <9 g/dL at screening or planned blood transfusions in the next 30 days
19. Serum potassium >5.5 mEq/L
20. Marked proteinuria suggestive of nephrotic syndrome
21. Estimated GFR (eGFR) as per MDRD equation <30 ml/min
22. Serum albumin of < 2.8 g/dL
23. Liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >5 times the upper limit of normal (ULN)
24. Total bilirubin >2.0 times ULN in the absence of Gilbert*s Syndrome
25. Known active hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, or diagnosis of immunodeficiency
26. Known active drug or alcohol abuse within 1 year of the Screening Visit at the discretion of the Investigator (i.e. 15 or more drinks for men per week or 8 or more for women).
27. Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or having received prior radiation therapy to the chest
28. Current or planned ultrafiltration, paracentesis, haemofiltration or dialysis
29. Currently receiving treatment with any intravenous steroid or > 5 mg of oral prednisone (or equivalent)
30. Recipient of stem cell or gene therapy or current therapeutic investigational devices
31. Participation in another clinical trial with an investigative prod
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change in NT-proBNP between Baseline and Day 8/Early Discharge</p><br>
- Secondary Outcome Measures
Name Time Method