An international study at different study sites testing the safety and effectiveness of a drug called BMS-986231 in the form of Intravenous Infusions for a duration of 48 hours in hospitalized patients whose heart is unable to pump sufficiently to maintain the blood flow their body needs to function well.
- Conditions
- Heart failure and impaired systolic functionMedDRA version: 20.0 Level: LLT Classification code 10074631 Term: Systolic heart failure System Organ Class: 100000004849MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-001685-29-GR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 310
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 < 140 kg at screening
j) Subject Re-Screening: This study permits the re-screening of a subject that has discontinued the study as a screen failure (has not been randomized).
3. Age and Reproductive Status
a) Males and Females, at least age 18 (or age of majority)
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 18 hours prior to the start of study treatment
c) Women must not be breastfeeding
d) WOCBP must agree to follow instruction for methods of contraception for 32 days after discontinuation (duration of study drug plus 30 days duration of one ovulatory cycle)
e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for 92 days after discontinuation (duration of study drug plus 90 days (duration of sperm turnover)
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section
Are the trial subjects under 18? no
1. Target Disease Exceptions
a) Systolic blood pressure (SBP) < 105 mm Hg or > 160 mm Hg at screening
b) Systolic blood pressure (SBP) < 105 mm Hg or > 160 mm Hg just prior to randomization
c) Heart rate < 50 beats per minute (bpm) or > 130 bpm at screening
d) Heart rate < 50 beats per minute (bpm) or > 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 < 6 months (eg, acute systemic infection – sepsis, metastatic cancer, or other serious illnesses)
g) Severe liver disease defined as history of cirrhosis with evidence of portal hypertension such as varices, or encephalopathy, or total bilirubin > 3 mg/dL (> 51 µmol/L)
h) Prior cardiac or renal transplant
3. Physical and Laboratory Test Findings
a) Have persistent abnormal serum electrolytes not resolved before randomization, as defined by any of the following:
i) A sodium (Na+) concentration < 130 or >145 mEq/L (mmol/L)
ii) A potassium (K+) concentration < 3.2 or >5.5 mEq/L (mmol/L)
b) Have severe anemia, as documented by a hemoglobin < 9 g/dL (< 5.59 mmol/L)
c) Have severe renal insufficiency before randomization (and during the current hospitalization) defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 [based on any standard limit and equation employed by the local lab, eg, Modification of Diet in Renal Disease (MDRD) equation]. For patients with eGFR values less than but close to 30 mL/min/1.73m2 upon testing, retesting is allowed
4. Prior and Concomitant Medications or Treatments
a) Subjects administered IV or transdermal nit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Up to 6 hours after the end of study drug infusion.;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.;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);<br> Secondary Objective: - Assess the effect of BMS-986231 on NT-proBNP<br> - Assess the effect of BMS-986231 on patient-reported resting dyspnea as measured by the 11-point Numerical Rating Scale (NRS)<br>
- Secondary Outcome Measures
Name Time Method <br> 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<br> - 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<br> ;<br> Timepoint(s) of evaluation of this end point: - Hour 24, 48, 72, 120 or discharge (whichever comes first), and at Day 32<br> <br> - baseline, and Hours 6, 12, 24, 48, and 72<br>