Clinical trial NCT03357731: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Cardiac Failure
Reduced Ventricular Ejection Fraction
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-11-30
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: at the end of the 5-hour infusion
Secondary outcomes:
measure: Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG
timeFrame: at the end of the 5-hour infusion
measure: Mean LVEF, Computed by Simpson's Method at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
timeFrame: at the end of the 5-hour infusion
measure: Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
timeFrame: at the end of the 5-hour infusion
measure: Mean Diastolic Indices: E/A and E/e' Ratio at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
timeFrame: at the end of the 5-hour infusion
measure: Mean Diastolic Indices: Annular e' Velocity at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
timeFrame: at the end of the 5-hour infusion
measure: Mean LV Global Longitudinal Strain, Computed Using STE at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
timeFrame: at the end of the 5-hour infusion
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine-Indianapolis
state: Indiana
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke Advanced Heart and Lung Failure Clinic
state: North Carolina
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Nagoya
country: Japan
facility: Local Institution
state: Aichi
city: Kawasaki
country: Japan
facility: Local Institution
state: Kanagawa
city: Suita-shi
country: Japan
facility: Local Institution
state: Osaka
city: Groiningen
country: Netherlands
facility: Local Institution
city: Edinburgh
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: Harrow
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
Study officials:
References:
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.