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

Primary Purpose

Heart Failure, Cardiac Failure, Reduced Ventricular Ejection Fraction

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
HNO Donor
Nitroglycerin (NTG)
Placebo
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Orange County Research Center
  • Northwestern Medicine
  • Indiana University School of Medicine-Indianapolis
  • Brigham and Womens Hospital
  • Duke Advanced Heart and Lung Failure Clinic
  • Inova Heart and Vascular Institute
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo/BMS-986231/NTG

Placebo/NTG/BMS-986231

NTG/Placebo/BMS-986231

NTG/BMS-986231/Placebo

BMS-986231/Placebo/NTG

BMS-986231/NTG/Placebo

Arm Description

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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
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
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
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

Full Information

First Posted
October 31, 2017
Last Updated
July 24, 2020
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03357731
Brief Title
A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
November 30, 2017 (Actual)
Primary Completion Date
May 10, 2019 (Actual)
Study Completion Date
May 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Cardiac Failure, Reduced Ventricular Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/BMS-986231/NTG
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Arm Title
Placebo/NTG/BMS-986231
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Arm Title
NTG/Placebo/BMS-986231
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Arm Title
NTG/BMS-986231/Placebo
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Arm Title
BMS-986231/Placebo/NTG
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Arm Title
BMS-986231/NTG/Placebo
Arm Type
Experimental
Arm Description
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Intervention Type
Drug
Intervention Name(s)
HNO Donor
Other Intervention Name(s)
BMS-986231
Intervention Description
Infusion
Intervention Type
Drug
Intervention Name(s)
Nitroglycerin (NTG)
Intervention Description
Infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
at the end of the 5-hour infusion
Secondary Outcome Measure Information:
Title
Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG
Description
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.
Time Frame
at the end of the 5-hour infusion
Title
Mean LVEF, Computed by Simpson's Method at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Description
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV ejection fraction
Time Frame
at the end of the 5-hour infusion
Title
Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Description
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Mean LV power index
Time Frame
at the end of the 5-hour infusion
Title
Mean Diastolic Indices: E/A and E/e' Ratio at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Description
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function
Time Frame
at the end of the 5-hour infusion
Title
Mean Diastolic Indices: Annular e' Velocity at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Description
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: Diastolic function
Time Frame
at the end of the 5-hour infusion
Title
Mean LV Global Longitudinal Strain, Computed Using STE at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Description
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG: LV global longitudinal strain
Time Frame
at the end of the 5-hour infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Northwestern Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University School of Medicine-Indianapolis
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-1218
Country
United States
Facility Name
Brigham and Womens Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Duke Advanced Heart and Lung Failure Clinic
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Inova Heart and Vascular Institute
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Local Institution
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Local Institution
City
Kawasaki
State/Province
Kanagawa
ZIP/Postal Code
211-8533
Country
Japan
Facility Name
Local Institution
City
Suita-shi
State/Province
Osaka
ZIP/Postal Code
5650871
Country
Japan
Facility Name
Local Institution
City
Groiningen
ZIP/Postal Code
9713GZ
Country
Netherlands
Facility Name
Local Institution
City
Edinburgh
ZIP/Postal Code
EH16 4SA
Country
United Kingdom
Facility Name
Local Institution
City
Glasgow
ZIP/Postal Code
G4 0SF
Country
United Kingdom
Facility Name
Local Institution
City
Glasgow
ZIP/Postal Code
G429LF
Country
United Kingdom
Facility Name
Local Institution
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Local Institution
City
Harrow
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Local Institution
City
London
ZIP/Postal Code
SE1 1YR
Country
United Kingdom
Facility Name
Local Institution
City
London
ZIP/Postal Code
sw17 0re
Country
United Kingdom
Facility Name
Local Institution
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31168885
Citation
Felker GM, Borentain M, Cleland JG, DeSouza MM, Kessler PD, O'Connor CM, Seiffert D, Teerlink JR, Voors AA, McMurray JJV. Rationale and design for the development of a novel nitroxyl donor in patients with acute heart failure. Eur J Heart Fail. 2019 Aug;21(8):1022-1031. doi: 10.1002/ejhf.1504. Epub 2019 Jun 6.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

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

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