A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Cross-over Phase 2 Study of Continuous 5-Hour Intravenous Infusions of BMS-986231 in Patients with Heart Failure and Impaired Systolic Functio
- Conditions
- chronic heart failure10019280
- Registration Number
- NL-OMON46654
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
* Signed Written Informed Consent
* Age 18 years (or age of majority) or older
* Heart failure with reduced ejection fraction (LVEF on echocardiogram of 40% or less), as assessed by the echocardiographic corelab.
* Stable guideline directed therapy for heart failure (could include oral diuretics, ACEi, ARBs, ARNi, MRAs , and * blockers as tolerated), with no dose changes of these medications in the past 2 weeks
* Have screening values of NT pro-BNP * 125 pg/mL (15 pmol/L) or BNP * 35 pg/mL (10 pmol/L).
* In sinus rhythm at the start of the infusion
* Body weight < 45 kg or * 140 kg
* Low quality echocardiographic visualization windows and image acquisition
* Systolic blood pressure (SBP) < 110 mm Hg at screening or pre-randomization
* Heart rate < 50 beats per minute (bpm) or > 90 bpm at screening or pre-randomization
* Permanent Atrial Fibrillation, Atrial Flutter or having Atrial Fibrillation, Atrial Flutter before start of the infusion
* Parmanent paced rhythm (VVI, DDD or BiV pacing)
* Ventricular assist device or prior heart transplant
* Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria.
* (Note: A restrictive mitral inflow pattern is NOT exclusionary)
* Large post-MI Left Ventricular aneurisms
* Intra-cardiac thrombus
* Prior mitral valve repair, mitral or aortic prosthesis
* Treatment with oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil, vardenafil or avanafil within 24 hours of study drug infusion or treated with tadalafil within 4 days of study drug infusion
* Hospitalized for acute decompensated heart failure in the previous month
* Hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening
* 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
* NYHA Class IV symptoms of heart failure
* Treatment with intravenous inotropic therapy (dobutamine, milrinone, leveosimendan) in the previous month or planned treatment in the next 3 months.
* Current treatment with chronic oral, transdermal or sublingual nitrates, except at the discretion of the investigator and treating physician, nitrates could be temporarily interrupted. In which case, an
interruption of 3 days is required prior to start of study drug.
* Prior solid organ transplant
* Estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2
* Have persistent abnormal serum electrolytes not resolved between screening and start of the study drug infusion, as defined by any of the following:
o A sodium (Na+) concentration < 130 or >145 mEq/L (mmol/L)
o A potassium (K+) concentration < 3.5 or >5.5 mEq/L (mmol/L)
* Have severe anemia, as documented by a hemoglobin < 9 g/dL (< 5.59 mmol/L)
* Liver disease defined as history of cirrhosis with evidence of portal hypertension such as varices, or encephalopathy, or total bilirubin > 3 mg/dL (> 51 *mol/L) or significant elevation of liver enzymes (AST, ALT > 3 times the upper limit of normal)
* Considered clinically unstable for any condition
* Serious comorbid non cardiovascular disease in which the life expectancy of the subject is < 3 months;Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb's approval is required.
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
c) Participation in an investigational clinical drug study within 30 days or 5 elimination half-lives, (whichever is longer) prior to randomization.
d) Prior particip
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Mean SVI derived from the velocity time integral at the left ventricular<br /><br>outflow tract (LVOT VTI) at the end of the 5-hours infusion of<br /><br>BMS-986231, versus placebo.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Mean SVI derived from LVOT VTI at the end of the 5-hours infusion of<br /><br>BMS-986231, versus NTG.<br /><br>* Mean LVEF, computed by Simpson*s method at the end of the 5-hours<br /><br>infusion of BMS-986231, versus placebo and NTG.<br /><br>* Mean cardiac power index at the end of the 5- hours infusion of<br /><br>BMS-986231, versus placebo and NTG.<br /><br>* Mean Diastolic indices: E/A, annular e' velocity and E/e' ratio at the<br /><br>end of the 5-hours infusion of BMS-986231, versus placebo and NTG.<br /><br>* Mean LV global longitudinal strain, computed using STE at the end of<br /><br>the 5-hours infusion of BMS-986231, versus placebo and NTG.</p><br>