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 Function
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 49
- Locations
- 7
- Primary Endpoint
- Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo
Study Overview
Brief Summary
The purpose of this study is to evaluate the effects of BMS-986231 on systolic and diastolic parameters in patients with heart failure and low ejection fraction.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Heart failure with reduced ejection fraction (LVEF on echocardiogram of 40% or less)
- •Stable guideline directed therapy for heart failure including oral diuretics, ACEi, ARBs, ARNi, MRAs, and β 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)
Exclusion Criteria
- •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
- •Estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2
- •Ventricular assist device or prior heart transplant
- •Prior solid organ transplant
- •Body weight < 45 kg or ≥ 140 kg
- •Low quality echocardiographic visualization windows and image acquisition
- •Permanent paced rhythm (VVI, DDD or BiV pacing)
- •Other protocol defined inclusion/exclusion criteria could apply
Arms & Interventions
BMS-986231/NTG/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
Placebo/BMS-986231/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
Placebo/BMS-986231/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
Placebo/BMS-986231/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
Placebo/NTG/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
Placebo/NTG/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
Placebo/NTG/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
NTG/Placebo/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
NTG/Placebo/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
NTG/Placebo/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
NTG/BMS-986231/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
NTG/BMS-986231/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
NTG/BMS-986231/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
BMS-986231/Placebo/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
BMS-986231/Placebo/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Nitroglycerin (NTG) (Drug)
BMS-986231/Placebo/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
BMS-986231/NTG/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: HNO Donor (Drug)
BMS-986231/NTG/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo
Time Frame: at the end of the 5-hour infusion
The objective is to evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to placebo.
Secondary Outcomes
- Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG(at the end of the 5-hour infusion)
- Mean Diastolic Indices: Annular e' Velocity at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG(at the end of the 5-hour infusion)
- Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG(at the end of the 5-hour infusion)
- Mean Diastolic Indices: E/A and E/e' Ratio at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG(at the end of the 5-hour infusion)
- Mean LV Global Longitudinal Strain, Computed Using STE at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG(at the end of the 5-hour infusion)
- Mean LVEF, Computed by Simpson's Method at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG(at the end of the 5-hour infusion)