Acute Decompensated Heart Failure Heart Disease
Conditions
Interventions
Patients will undergo screening tests and assessments to determine eligibility.
Those eligible to participate in the study will be randomised to the treatment
arm or the placebo-controlled arm in a
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Patients currently hospitalized for ADHF, regardless of Left Ventricular Ejection Fraction (LVEF) 24 hours or greater since presentation to the Emergency Room defined as the time of the first dose of IV diuretic administered at the hospital, maximum of 8 days since presentation to ER and before hospital discharge. * Acute Decompensated Heart Failure is the main reason for admission and there is no other potential cause for congestive symptoms leading to index hospitalization (eg, concurrent pneumonia, acute COPD exacerbation) * Dyspnea at rest or with minimal exertion upon presentation to ER, plus signs and symptoms of fluid overload that require IV therapy with loop diuretics * NT-proBNP greater than or equal to 1400 pg/mL OR BNP greater than or equal to 350 pg/mL upon presentation to the hospital; NT-proBNP greater than or equal to 2000 pg/mL OR BNP greater than or equal to 500 pg/mL if Atrial Fibrillation (AFib) present at presentation. For participants on Entresto, NT-proBNP should be used. * Patients must be hemodynamically stable, as assessed by the investigator, and as defined by the following criteria: - * 12 hours since the last dose change of IV loop diuretics (ie, participants may still be on IV loop diuretics at randomization, as long as dose is stable for 12 hours or greater). - * 24 hours since last dose of positive inotropes. - * 12 hours since the last dose of IV vasodilators. - Absence of symptoms of hypotension (eg, dizziness, lightheadedness, etc), - Supine Systolic Blood Pressure (SBP) must remain within the following range*, on at least 2 routine consecutive measurements, over the 12 hours before randomization: 1.) Sentinel Group: SBP greater than or equal to 115 mmHg 2.) Main Group: SBP greater than or equal to 100 mmHg * Males and Females at least 18 years of age * Males who are sexually active with Woman of Child-Bearing Potential (WOCBP) must agree to follow instructions for method(s) of contraception defined in the protocol, during the study and for at least 6 days after the last dose of the study treatment * Female Participants: - Are eligible to participate if they are not pregnant or breast feeding and if they are not a WOCBP - Women must have documented proof that they are not of childbearing potential
Exclusion criteria
Exclusion criteria: * At randomisation Systolic Blood Pressure (SBP) less than 100 mmHg or greater than 145 mmHg * At randomisation Heart Rate (HR) greater than 120 bpm * Acute cardiovascular condition other than HF decompensation either contributing to hospitalisation or making the participant unstable, such as acute MI/acute coronary syndrome, myocarditis, or arrhythmia with the exception of atrial fibrillation if HR within criteria limit. * Cardiogenic shock (defined as SBP below 90 mmHg, signs of end-organ hypoperfusion plus need for intubation, mechanical circulatory support and other life-sustaining emergency measures) at presentation to Emergency Room or at any time before randomisation. * History of heart or any other solid organ transplant or currently on the transplant list. * Recipient of ventricular assist devices. * Use of any cardiac extracorporeal devices, within 12 weeks of study randomisation. Cardiac Resynchronization Therapy Defibrillator (CRTD) and pacemakers / Implantable Cardioverter-Defibrillator (ICDs) are allowed, if implanted at least 4 weeks before randomization and no discharge within 4 weeks prior to randomisation. * Participants with contraindications to vasodilator therapy such as restrictive or obstructive cardiomyopathy, severe mitral or aortic stenosis. * Women cannot be pregnant or breastfeeding. * Any major surgery within 12 weeks of study randomization. * Suspected acute pulmonary disease such as pneumonia, exacerbation of asthma or COPD or severe chronic, pulmonary disease (eg. severe COPD , pulmonary fibrosis, patients with hypercapnia or requiring home oxygen or chronic systemic steroids). * Hereditary or idiopathic pulmonary hypertension. * History of stroke, or transient ischemic attack (TIA) within the 30 days prior to screening (according to the participants' records) or during screening. * Acute coronary event within 30 days prior to screening or during screening (myocardial infarction, acute coronary syndrome, or unstable angina; according to the participants' records). * Terminal non-cardiovascular disease such as cancer with a life expectancy for less than 6 months. * Severe liver disease such as cirrhosis with evidence of portal hypertension, or acute viral hepatitis. * Participant is on dialysis or history of chronic or intermittent dialysis or ultrafiltration. * Need for mechanical ventilation any time before screening or non-invasive ventilation (CPAP, BiPAP) less than 2 hrs prior to screening. * Inability to comply with restrictions and prohibited treatments as listed in the protocol. * Exposure to any investigational drug or placebo, including serelaxin; within 30 days of initial study drug administration or 4 months prior to the first dose of investigational product, in case of exposure to long-acting biological investigational drug. * Persistent electrolytes abnormalities not corrected before randomization - (1) A sodium concentration less than 130 or greater than 145 mEq/l - (2) A potassium concentration less than 3.1 or greater than 5.5 mEq/l * Haemoglobin less than 9 g/dL, which is defined as severe anaemia. * eGFR less than 30 ml/min./1.73 m2. * Liver abnormalities including total bilirubin greater than 2 mg/dL (greater than 34.2 micromol/L) or significant elevation of liver enzymes (AST, ALT greate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to establish the safety and tolerability of BMS-986259 study drug when initiated in hospital in-patients, who are medically stable after an admission for Acute Decompensated Heart Failure. The outcome will be measured by the incidence of clinically relevant hypotension. This is defined as: - Supine Systolic Blood Pressure less than 85mmHg (confirmed by repeat measurement within 30 minutes) regardless of symptoms OR - Supine Systolic Blood Pressure less than 90mmHg (confirmed by repeat measurement within 30 minutes) AND symptoms of Hypotension. | — |
Secondary
| Measure | Time frame |
|---|---|
| *The secondary objective of this study is to evaluate serum PK parameters in participants with Heart Failure. This outcome will be measured by trough PK sampling on day 5 including: serum PK parameters Cmax, Tmax, Area Under the Curve (AUC) and C24. Additional objectives will be: *To explore the potential diuretic effects of BMS-986259 study drug. This will be assessed by measuring the change from baseline in natriuresis after IV loop diuretic administration. The total and daily dose of loop diuretics administered during the study will be collected. *To explore biomarkers related to the mechanism of action of BMS-986259 and related physiolocigal changes which cause Heart Failure. These may include but are not limited to Troponin, NT-proBNP, ST2, eGFR, cystatin C, aldosterone, urine creatinine, urine electrolytes, collagen markers such as ProC6. This will be explored by measuring the change from baseline in these biomarker levels, in blood and urine. *To evaluate the presence of Anti-Drug Antibodies(ADA) and Neutralising Antibodies(nAb). These antibodies may effect movement of BMS-986259 (relaxin) through the body or cancel-out the therapeutic effects of the study treatment. These will be measured through blood sample collection. *To evaluate blood pressure changes during daytime and night time. This will be measured and compared between the two arms (treatment vs placebo) using a 48 hours Ambulatory Blood pressure monitor device. The device will measure mean ambulatory Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), in addition to daytime and night time mean SBP and DBP. *To explore patient reported outcomes. These will be measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score from baseline (Day 1 of treatment), at the end of treatment (Day 14) and follow-up (Day 30). | — |
Countries
Netherlands
Outcome results
None listed