Clinical trial NCT03730961: An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic
Official title: A Randomized, Double-Blind, Placebo-Controlled, Cross-over Phase 2 Study of Continuous 8-Hour Intravenous Infusions of BMS-986231 in Patients With Heart Failure and Impaired Systolic Function Given a Standard Dose of Loop Diuretic
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Failure
Myocardial Failure
Congestive Heart Failure
Heart Decompensation
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2018-11-05
Enrollment: 23
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 investigate continuous 8-hour introductions of BMS-986231 in participants with heart failure and weakened heart function given a standard dose of diuretic.


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Left ventricular ejection fraction \<45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan within 18 months
* On stable chronic guideline-directed therapy for HF including chronic loop diuretics, ACEi, ARBs, MRAs, ARNI or / and β-blockers as tolerated, with no changes of these medications in the past 2 weeks
* At least an oral dose of 40 mg of furosemide/day or equivalent (20 mg torsemide, 1 mg bumetamide)

Exclusion Criteria:

* SBP \< 115 mm Hg or \> 180 mm Hg at screening or pre-randomization
* Heart rate \< 50 beats per minute (bpm) or \> 120 bpm at screening or pre-randomization
* Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo
timeFrame: 4 hours
Secondary outcomes:
measure: FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo
timeFrame: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
measure: FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo
timeFrame: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
measure: Furosemide Urinary Concentrations
timeFrame: Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours
measure: Furosemide Plasma Concentrations
timeFrame: Day 1: 4, 5, 6, 8, 10 hours
measure: Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion
timeFrame: 0-4 hours after furosemide
measure: Number of Participants With Clinically Relevant Hypotension
timeFrame: up to 8 hours
measure: Number of Participants With an Adverse Event (AE)
timeFrame: up to 8 days
measure: Number of Participants With an Abnormal Clinical Laboratory Value
timeFrame: from first dose to 30 days post-last dose (ca. 5-8 weeks)
measure: Change From Baseline in Vital Signs - Blood Pressure
timeFrame: Day 1, 8 hours post-dose (end of infusion)
measure: Change From Baseline in Vital Signs - Heart Rate
timeFrame: Day 1, 8 hours post-dose (end of infusion)
measure: Change From Baseline in Vital Signs - Oxygen Saturation
timeFrame: Day 1, 8 hours post-dose (end of infusion)
measure: Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate
timeFrame: Day 1, 8 hours post-dose (end of infusion)
measure: Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals
timeFrame: Day 1, 8 hours post-dose (end of infusion)
measure: Telemetry
timeFrame: Day 1, 8 hours post-dose
measure: Change From Baseline in Physical Examination - Body Weight
timeFrame: Day 1, 8 hours post-dose (end of infusion)
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Glasgow Clinical Research Facility
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
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.