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

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ClinicalTrials.gov Identifier: NCT03357731
Recruitment Status : Completed
First Posted : November 30, 2017
Results First Posted : July 27, 2020
Last Update Posted : July 27, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Heart Failure Cardiac Failure Reduced Ventricular Ejection Fraction Drug: HNO Donor Drug: Nitroglycerin (NTG) Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2017
Actual Primary Completion Date : May 10, 2019
Actual Study Completion Date : May 10, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: BMS-986231

Drug: Nitroglycerin (NTG)
Infusion

Other: Placebo
Infusion




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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


  3. 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


  4. 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


  5. 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


  6. 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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03357731


Locations
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United States, California
Orange County Research Center
Tustin, California, United States, 92780
United States, Illinois
Northwestern Medicine
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University School of Medicine-Indianapolis
Indianapolis, Indiana, United States, 46202-1218
United States, Massachusetts
Brigham and Womens Hospital
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Advanced Heart and Lung Failure Clinic
Durham, North Carolina, United States, 27710
United States, Virginia
Inova Heart and Vascular Institute
Falls Church, Virginia, United States, 22042
Japan
Local Institution
Nagoya, Aichi, Japan, 466-8560
Local Institution
Kawasaki, Kanagawa, Japan, 211-8533
Local Institution
Suita-shi, Osaka, Japan, 5650871
Netherlands
Local Institution
Groiningen, Netherlands, 9713GZ
United Kingdom
Local Institution
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
Sponsors and Collaborators
Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Statistical Analysis Plan  [PDF] December 6, 2017
Study Protocol  [PDF] January 24, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03357731    
Other Study ID Numbers: CV013-020
2016-003586-26 ( EudraCT Number )
First Posted: November 30, 2017    Key Record Dates
Results First Posted: July 27, 2020
Last Update Posted: July 27, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Nitroglycerin
Vasodilator Agents