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Completed

NCT Number: 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

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.

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Key information

Conditions

Cardiac Failure Cardiovascular Diseases Congestive Heart Failure Heart Decompensation Heart Diseases Heart Failure Myocardial Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Glasgow Clinical Research Facility, Glasgow, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BMS-986231

Drug

Intravenous administration

Furosemide

Drug

Intravenous administration

Placebo

Drug

Intravenous administration

Primary outcomes

  1. 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo

    Time frame: 4 hours

    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

Secondary outcomes

  1. FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo

    Time frame: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours

    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

  2. FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo

    Time frame: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours

    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

  3. Furosemide Urinary Concentrations

    Time frame: Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours

    Summary of urine recovery by interval, measured by amount excreted.

  4. Furosemide Plasma Concentrations

    Time frame: Day 1: 4, 5, 6, 8, 10 hours

    Summary of plasma concentrations by interval.

  5. Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion

    Time frame: 0-4 hours after furosemide

    Summary of urinary concentrations 0-4 hours after furosemide

    Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine

  6. Number of Participants With Clinically Relevant Hypotension

    Time frame: up to 8 hours

    Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion

  7. Number of Participants With an Adverse Event (AE)

    Time frame: up to 8 days

    Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion

  8. Number of Participants With an Abnormal Clinical Laboratory Value

    Time frame: from first dose to 30 days post-last dose (ca. 5-8 weeks)

    Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis.

  9. Change From Baseline in Vital Signs - Blood Pressure

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for vital signs was reported for each arm.

  10. Change From Baseline in Vital Signs - Heart Rate

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for vital signs was reported for each arm.

  11. Change From Baseline in Vital Signs - Oxygen Saturation

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for vital signs was reported for each arm.

  12. Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for ECGs was reported for each arm.

  13. Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for ECGs was reported for each arm.

  14. Telemetry

    Time frame: Day 1, 8 hours post-dose

    Telemetry data not collected.

  15. Change From Baseline in Physical Examination - Body Weight

    Time frame: Day 1, 8 hours post-dose (end of infusion)

    The change in baseline for physical examinations was reported for each arm.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2019
Study completion
2020
First posted
Nov 5, 2018
Registry last updated
Feb 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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