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

Congestive Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03730961
• Other study ID #: CV013-034
• Secondary ID: 2018-000970-31
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2019
• Est. completion date: January 9, 2020

Study information

• Verified date: February 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 9, 2020
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Cardiac Failure
• Congestive Heart Failure
• Heart Decompensation
• Heart Failure
• Myocardial Failure

Intervention

Drug:
• BMS-986231
Intravenous administration
• Furosemide
Intravenous administration
• Placebo
Intravenous administration

Locations

Country	Name	City	State
United Kingdom	Glasgow Clinical Research Facility	Glasgow
United Kingdom	Richmond Pharmacology	London

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo	The total volume of urinary output 4 hours after 40 mg furosemide bolus given to participants with HFrEF while on BMS-986231 compared to placebo: absolute difference in total volume and % change from placebo.; Sequence 1: Placebo in period 1, drug in period 2; Sequence 2: Drug in period 1, placebo in period 2	4 hours
Secondary	FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo	Secondary efficacy analyses was performed using the randomized population. The FeNa, FeK, furosemide urinary and plasma concentration and the ratio of urinary sodium to urinary furosemide was calculated at each time point over 4-hour urine/plasma collection after a bolus injection of 40 mg furosemide while receiving BMS-986231 or placebo.; Fractional Excretion Na = ((Urine Sodium * Plasma Creatinine) / (Plasma Sodium * Urine Creatinine)) * 100	Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
Secondary	FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo	Secondary efficacy analyses was performed using the randomized population. The FeNa, FeK, furosemide urinary and plasma concentration and the ratio of urinary sodium to urinary furosemide was calculated at each time point over 4-hour urine/plasma collection after a bolus injection of 40 mg furosemide while receiving BMS-986231 or placebo.; Fractional Excretion K = ((Urine Potassium * Plasma Creatinine) / (Plasma Potassium * Urine Creatinine)) * 100	Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
Secondary	Furosemide Urinary Concentrations	Summary of urine recovery by interval, measured by amount excreted.	Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours
Secondary	Furosemide Plasma Concentrations	Summary of plasma concentrations by interval.	Day 1: 4, 5, 6, 8, 10 hours
Secondary	Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion	Summary of urinary concentrations 0-4 hours after furosemide; Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine	0-4 hours after furosemide
Secondary	Number of Participants With Clinically Relevant Hypotension	Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion	up to 8 hours
Secondary	Number of Participants With an Adverse Event (AE)	Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion	up to 8 days
Secondary	Number of Participants With an Abnormal Clinical Laboratory Value	Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis.	from first dose to 30 days post-last dose (ca. 5-8 weeks)
Secondary	Change From Baseline in Vital Signs - Blood Pressure	The change in baseline for vital signs was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)
Secondary	Change From Baseline in Vital Signs - Heart Rate	The change in baseline for vital signs was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)
Secondary	Change From Baseline in Vital Signs - Oxygen Saturation	The change in baseline for vital signs was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)
Secondary	Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate	The change in baseline for ECGs was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)
Secondary	Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals	The change in baseline for ECGs was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)
Secondary	Telemetry	Telemetry data not collected.	Day 1, 8 hours post-dose
Secondary	Change From Baseline in Physical Examination - Body Weight	The change in baseline for physical examinations was reported for each arm.	Day 1, 8 hours post-dose (end of infusion)

External Links

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