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

July 24, 2020 updated by: Bristol-Myers Squibb

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 466-8560
        • Local Institution
    • Kanagawa
      • Kawasaki, Kanagawa, Japan, 211-8533
        • Local Institution
    • Osaka
      • Suita-shi, Osaka, Japan, 5650871
        • Local Institution
  • Netherlands
      • Groiningen, Netherlands, 9713GZ
        • Local Institution
  • United Kingdom
      • Edinburgh, United Kingdom, EH16 4SA
        • Local Institution
      • Glasgow, United Kingdom, G4 0SF
        • Local Institution
      • Glasgow, United Kingdom, G429LF
        • Local Institution
      • Glasgow, United Kingdom, G51 4TF
        • Local Institution
      • Harrow, United Kingdom, HA1 3UJ
        • Local Institution
      • London, United Kingdom, SE1 1YR
        • Local Institution
      • London, United Kingdom, sw17 0re
        • Local Institution
      • London, United Kingdom, SW3 6NP
        • Local Institution
  • United States
    • California
      • Tustin, California, United States, 92780
        • Orange County Research Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202-1218
        • Indiana University School of Medicine-Indianapolis
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Womens Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Advanced Heart and Lung Failure Clinic
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Heart and Vascular Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Placebo/BMS-986231/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion
EXPERIMENTAL: Placebo/NTG/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion
EXPERIMENTAL: NTG/Placebo/BMS-986231
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion
EXPERIMENTAL: NTG/BMS-986231/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion
EXPERIMENTAL: BMS-986231/Placebo/NTG
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion
EXPERIMENTAL: BMS-986231/NTG/Placebo
administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Drug: HNO Donor
Infusion
Other Names:
  • BMS-986231
Drug: Nitroglycerin (NTG)
Infusion
Other: Placebo
Infusion

What is the study measuring?

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
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.
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
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 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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
at the end of the 5-hour infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 30, 2017

Primary Completion (ACTUAL)

May 10, 2019

Study Completion (ACTUAL)

May 10, 2019

Study Registration Dates

First Submitted

October 31, 2017

First Submitted That Met QC Criteria

November 29, 2017

First Posted (ACTUAL)

November 30, 2017

Study Record Updates

Last Update Posted (ACTUAL)

July 27, 2020

Last Update Submitted That Met QC Criteria

July 24, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CV013-020
  • 2016-003586-26 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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