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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

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ClinicalTrials.gov Identifier: NCT03730961
Recruitment Status : Completed
First Posted : November 5, 2018
Results First Posted : January 26, 2021
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Cardiac Failure Myocardial Failure Congestive Heart Failure Heart Decompensation Drug: BMS-986231 Drug: Furosemide Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 17, 2019
Actual Primary Completion Date : December 11, 2019
Actual Study Completion Date : January 9, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Placebo+Diuretic to BMS-986231+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
Drug: BMS-986231
Intravenous administration

Drug: Furosemide
Intravenous administration

Drug: Placebo
Intravenous administration

Experimental: BMS-986231+Diuretic to Placebo+Diuretic
Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
Drug: BMS-986231
Intravenous administration

Drug: Furosemide
Intravenous administration

Drug: Placebo
Intravenous administration




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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:

  • 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


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): NCT03730961


Locations
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United Kingdom
Glasgow Clinical Research Facility
Glasgow, United Kingdom, G51 4TF
Richmond Pharmacology
London, United Kingdom, SW17 0RE
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] April 15, 2019
Statistical Analysis Plan  [PDF] January 22, 2020

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: NCT03730961    
Other Study ID Numbers: CV013-034
2018-000970-31 ( EudraCT Number )
First Posted: November 5, 2018    Key Record Dates
Results First Posted: January 26, 2021
Last Update Posted: February 26, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Furosemide
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action