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

Phase 2

Completed

• Conditions: Heart Failure; Cardiac Failure; Reduced Ventricular Ejection Fraction
• Interventions: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo

• Registration Number: NCT03357731
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-10-31
• Study First Submitted QC: 2017-11-29
• Study Start: 2017-11-30
• Study First Posted: 2017-11-30
• Primary Completion: 2019-05-10
• Study Completion: 2019-05-10
• Results First Submitted: 2020-05-06
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-24
• Last Update Submitted: 2020-07-24
• Results First Posted: 2020-07-27
• Last Update Posted: 2020-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BMS-986231/Placebo/NTG	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/NTG/Placebo	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/NTG/BMS-986231	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/Placebo/NTG	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/Placebo/NTG	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/BMS-986231/Placebo	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/NTG/BMS-986231	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/NTG/Placebo	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/NTG/BMS-986231	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/Placebo/BMS-986231	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/NTG/Placebo	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/BMS-986231/NTG	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/Placebo/BMS-986231	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/Placebo/BMS-986231	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/BMS-986231/Placebo	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/BMS-986231/NTG	HNO Donor	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/BMS-986231/NTG	Placebo	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/BMS-986231/Placebo	Nitroglycerin (NTG)	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

Primary Outcome Measures

Name	Time	Method
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	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 Outcome Measures

Name	Time	Method
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	Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Mean LV power index
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	Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function
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	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.
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	Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function
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	Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV global longitudinal strain
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	Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV ejection fraction

Trial Locations

Locations (7)

Orange County Research Center; 🇺🇸 Tustin, California, United States

Brigham and Womens Hospital; 🇺🇸 Boston, Massachusetts, United States

Inova Heart and Vascular Institute; 🇺🇸 Falls Church, Virginia, United States

Local Institution; 🇬🇧 London, United Kingdom

Northwestern Medicine; 🇺🇸 Chicago, Illinois, United States

Indiana University School of Medicine-Indianapolis; 🇺🇸 Indianapolis, Indiana, United States

Duke Advanced Heart and Lung Failure Clinic; 🇺🇸 Durham, North Carolina, United States