A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Reduced Ventricular Ejection Fraction, Heart Failure, Cardiac Failure

Intervention / Treatment
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* Drug: HNO Donor
* Drug: Nitroglycerin (NTG)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo/BMS-986231/NTG<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|
| Experimental: Placebo/NTG/BMS-986231<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|
| Experimental: NTG/Placebo/BMS-986231<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|
| Experimental: NTG/BMS-986231/Placebo<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|
| Experimental: BMS-986231/Placebo/NTG<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|
| Experimental: BMS-986231/NTG/Placebo<br>administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods | Drug: HNO Donor<br>* Infusion<br>* Other names: BMS-986231;Drug: Nitroglycerin (NTG)<br>* Infusion<br>Other: Placebo<br>* Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | at the end of the 5-hour infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG | 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 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 | Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV ejection fraction | at the end of the 5-hour infusion | 
| Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG | Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Mean LV power index | 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 | Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function | 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 | Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function | 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 | Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV global longitudinal strain | at the end of the 5-hour infusion |