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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03357731
• Other study ID #: CV013-020
• Secondary ID: 2016-003586-26
• Status: Completed
• Phase: Phase 2
• Start date: November 30, 2017
• Est. completion date: May 10, 2019

Study information

• Verified date: July 2020
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: May 10, 2019
• Est. primary completion date: May 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß 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

Related Conditions & MeSH terms

• Cardiac Failure
• Heart Failure
• Reduced Ventricular Ejection Fraction

Intervention

Drug:
• HNO Donor
Infusion
• Nitroglycerin (NTG)
Infusion

Other:
• Placebo
Infusion

Locations

Country	Name	City	State
Japan	Local Institution	Kawasaki	Kanagawa
Japan	Local Institution	Nagoya	Aichi
Japan	Local Institution	Suita-shi	Osaka
Netherlands	Local Institution	Groiningen
United Kingdom	Local Institution	Edinburgh
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	Harrow
United Kingdom	Local Institution	London
United Kingdom	Local Institution	London
United Kingdom	Local Institution	London
United States	Brigham and Womens Hospital	Boston	Massachusetts
United States	Northwestern Medicine	Chicago	Illinois
United States	Duke Advanced Heart and Lung Failure Clinic	Durham	North Carolina
United States	Inova Heart and Vascular Institute	Falls Church	Virginia
United States	Indiana University School of Medicine-Indianapolis	Indianapolis	Indiana
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Japan,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form