Heart failure and impaired systolic function MedDRA version: 20.0 Level: LLT Classification code 10074631 Term: Systolic heart failure System Organ Class: 100000004849 MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: HNO donor
Product Code: BMS-986231
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: HNO
CAS Number: 1620330-72-4
Current Sponsor code: CV013-011
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Written Informed Consent a) Subjects will be required to provide a written informed consent 2. Target Population b) Subjects being hospitalized for ADHF c) Have had at least 1 administration of at least 40 mg furosemide intravenous, or equivalent (e.g 40 mg furosemide equivalent to 20 mg torsemide or to 1 mg bumetanide) for the current ADHF episode d) Subject must be randomized and treated within 18 hours of first dose of intravenous diuretic e) Have dyspnea at rest or with minimal exertion after administration of at least 1 dose of intravenous diuretics. Subject must not be randomized within 2 hours after an IV bolus dose of intravenous diuretics, or within 2 hours after the initiation or a dose increase of an IV diuretic administered by continuous infusion f) Have a history of heart failure and a left ventricular ejection fraction (LVEF) = 40%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan Note: Ejection fraction documentation up to 18 months prior to screening may be used if there is no clinical expectation of improvement in ejection fraction in that timeframe (eg, the patient has not had biventricular pacing initiated during that period) g) Have at least 2 of the following at time of screening: i) evidence for pulmonary congestion on chest x-ray ii) rales by chest auscultation, iii) edema = 2+ on a 0 to 3+ scale (easily identifiable indentation, skin rebounds in 15-30 seconds) iv) presence of jugular venous distention h) Have an elevated NT-proBNP = 1600 pg/mL (189 pmol/L) or BNP = 400 pg/mL (116 pmol/L) as determined at the local laboratory within 18 hours prior to the start of study drug infusion For subjects with atrial fibrillation: NT-proBNP = 2400 pg/ml or BNP =? 600 pg/ml i) Body weight = 50 kg and =65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: 1. Target Disease Exceptions a) Systolic blood pressure (SBP) 160 mm Hg at screening b) Systolic blood pressure (SBP) 160 mm Hg just prior to randomization c) Heart rate 130 bpm at screening d) Heart rate 130 bpm just prior to randomization e) Have a primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria Note: Functional mitral regurgitation, as well as restrictive mitral inflow pattern on echocardiography is not exclusionary f) Have a body temperature = 38.5°C (101.3°F) at any time from screening to randomization g) Have an active infection requiring IV anti-microbial treatment 2. Medical History and Concurrent Diseases a) Considered clinically unstable for other conditions than acute heart failure, either because of acute coronary syndrome or ongoing arrhythmia (or be receiving concomitant parenteral therapy with any antiarrhythmic drugs), or other unstable non-cardiovascular disease b) Severe chronic or acute lung disease that might interfere with the ability to interpret the dyspnea assessments (eg, severe chronic obstructive pulmonary disease, active asthma or acute pneumonia) c) Have a history of sudden cardiac death with resuscitation within the past 6 months d) Be hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening e) Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening f) Serious comorbid non cardiovascular disease in which the life expectancy of the subject is 3 mg/dL (> 51 µmol/L), or elevated AST or elevated ALT 145 mEq/L (mmol/L) ii) A potassium (K+) concentration 5.5 mEq/L (mmol/L) b) Have severe anemia, as documented by a hemoglobin 120 mm Hg AND ii) The IV nitroglycerin dose is 2 hours b) History of chronic or intermittent renal support therapy (hemodialysis, ultrafiltration, or peritoneal dia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effects of various doses of BMS-986231 compared to placebo on clinically relevant hypotension (defined by SBP < 90 mm Hg or symptoms of hypotension);Secondary Objective: - Assess the effect of BMS-986231 on NT-proBNP - Assess the effect of BMS-986231 on patient-reported resting dyspnea as measured by the 11-point Numerical Rating Scale (NRS);Primary end point(s): The primary endpoint is the incidence of clinically relevant hypotension, defined by SBP < 90 mm Hg (confirmed by a repeated value < 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion.;Timepoint(s) of evaluation of this end point: Up to 6 hours after the end of study drug infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in NT-proBNP from baseline to Hour 24, 48, 72, 120 or discharge (whichever comes first), and at Day 32 - Change in subject-reported resting dyspnea from baseline through Hour 72, as measured by the area under the curve (AUC) of the 11-point Numerical Rating Scale (NRS) obtained at baseline, and Hours 6, 12, 24, 48, and 72;Timepoint(s) of evaluation of this end point: - Hour 24, 48, 72, 120 or discharge (whichever comes first), and at Day 32 - baseline, and Hours 6, 12, 24, 48, and 72 | — |
Countries
Argentina, Canada, Czech Republic, France, Germany, Greece, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed