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

NCT03730961 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CV013-0342018-000970-31
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

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.

Conditions

Cardiac Failure; Myocardial Failure; Congestive Heart Failure; Heart Decompensation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

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

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

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

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

• Furosemide Urinary Concentrations

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

• Furosemide Plasma Concentrations

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

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

  0-4 hours after furosemide

Study Arms (2)

Placebo+Diuretic to BMS-986231+Diuretic

EXPERIMENTAL

Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods

Drug: BMS-986231; Drug: Furosemide; Drug: Placebo

BMS-986231+Diuretic to Placebo+Diuretic

EXPERIMENTAL

Administered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods

Drug: BMS-986231; Drug: Furosemide; Drug: Placebo

Interventions

BMS-986231 DRUG

Intravenous administration

BMS-986231+Diuretic to Placebo+Diuretic; Placebo+Diuretic to BMS-986231+Diuretic

Furosemide DRUG

Intravenous administration

BMS-986231+Diuretic to Placebo+Diuretic; Placebo+Diuretic to BMS-986231+Diuretic

Placebo DRUG

Intravenous administration

BMS-986231+Diuretic to Placebo+Diuretic; Placebo+Diuretic to BMS-986231+Diuretic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (2)

Glasgow Clinical Research Facility

Glasgow, G51 4TF, United Kingdom

Location

Richmond Pharmacology

London, SW17 0RE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31168885 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 5, 2018
• Study Start: January 17, 2019
• Primary Completion: December 11, 2019
• Study Completion: January 9, 2020
• Last Updated: February 26, 2021
• Results First Posted: January 26, 2021

Record last verified: 2021-02

Locations

GB (2)