Cardiac FailurePhase 2NCT03730961

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

A Phase 2 study testing BMS-986231 and Furosemide in people with Cardiac Failure and Myocardial Failure, run by Bristol-Myers Squibb at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cardiac Failure, Myocardial Failure, Congestive Heart Failure
What is being tested?: BMS-986231 and Furosemide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 23 participants
Where: 2 sitesUnited Kingdom
Study dates: 17 Jan 2019to 9 Jan 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

Glasgow Clinical Research Facility
Glasgow, G51 4TF
Richmond Pharmacology
London, SW17 0RE

Other trials in United Kingdom

About this study

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

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
Being tested: BMS-986231, Furosemide, Placebo
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BMS-986231Drug
Intravenous administration
FurosemideDrug
Intravenous administration
PlaceboDrug
Intravenous administration

Study groups in NCT03730961
Study group	Role	What they receive
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 Receives: 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 Receives: Drug: BMS-986231; Drug: Furosemide; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 4 hours

Secondary outcomes (15)

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
Measured: 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
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
Measured: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
Furosemide Urinary Concentrations
Summary of urine recovery by interval, measured by amount excreted.
Measured: 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
Summary of plasma concentrations by interval.
Measured: Day 1: 4, 5, 6, 8, 10 hours
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
Measured: 0-4 hours after furosemide
Number of Participants With Clinically Relevant Hypotension
Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion
Measured: up to 8 hours
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
Measured: up to 8 days
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.
Measured: from first dose to 30 days post-last dose (ca. 5-8 weeks)
Change From Baseline in Vital Signs - Blood Pressure
The change in baseline for vital signs was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Vital Signs - Heart Rate
The change in baseline for vital signs was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Vital Signs - Oxygen Saturation
The change in baseline for vital signs was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate
The change in baseline for ECGs was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals
The change in baseline for ECGs was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)
Telemetry
Telemetry data not collected.
Measured: Day 1, 8 hours post-dose
Change From Baseline in Physical Examination - Body Weight
The change in baseline for physical examinations was reported for each arm.
Measured: Day 1, 8 hours post-dose (end of infusion)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Jan 20199 Jan 2020

First posted5 Nov 2018
Study start17 Jan 2019
Primary completion11 Dec 2019
Study completion9 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cardiac FailureStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03730961
Sponsor's protocol ID: CV013-034
Other IDs: 2018-000970-31, 2018
Status last verified: Feb 2021
First submitted: 1 Nov 2018
Last updated: 26 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 31168885

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

All Cardiac Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03730961
Acronym / sponsor ID: CV013-034
Conditions: Cardiac Failure, Myocardial Failure, Congestive Heart Failure, Heart Decompensation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: 17 Jan 2019 (actual)
Primary completion: 11 Dec 2019 (actual)
Study completion: 9 Jan 2020 (actual)
First posted: 5 Nov 2018 (actual)
Results: Posted 26 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Placebo+Diuretic to BMS-986231+Diuretic	Experimental	Drug: BMS-986231, Drug: Furosemide, Drug: PlaceboAdministered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods
BMS-986231+Diuretic to Placebo+Diuretic	Experimental	Drug: BMS-986231, Drug: Furosemide, Drug: PlaceboAdministered in a cross over design with 8-hour continuous infusions and 7-28 day wash-out periods

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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)

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BMS-986231Intravenous administration	Drug	BMS-986231+Diuretic to Placebo+Diuretic, Placebo+Diuretic to BMS-986231+Diuretic
FurosemideIntravenous administration	Drug	BMS-986231+Diuretic to Placebo+Diuretic, Placebo+Diuretic to BMS-986231+Diuretic
PlaceboIntravenous administration	Drug	BMS-986231+Diuretic to Placebo+Diuretic, Placebo+Diuretic to BMS-986231+Diuretic

Primary outcome

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

15 secondary outcomes

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
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
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
Furosemide Plasma Concentrations
Time frame: Day 1: 4, 5, 6, 8, 10 hours
Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion
Time frame: 0-4 hours after furosemide
Number of Participants With Clinically Relevant Hypotension
Time frame: up to 8 hours
Number of Participants With an Adverse Event (AE)
Time frame: up to 8 days
Number of Participants With an Abnormal Clinical Laboratory Value
Time frame: from first dose to 30 days post-last dose (ca. 5-8 weeks)
Change From Baseline in Vital Signs - Blood Pressure
Time frame: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Vital Signs - Heart Rate
Time frame: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Vital Signs - Oxygen Saturation
Time frame: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate
Time frame: Day 1, 8 hours post-dose (end of infusion)
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals
Time frame: Day 1, 8 hours post-dose (end of infusion)
Telemetry
Time frame: Day 1, 8 hours post-dose
Change From Baseline in Physical Examination - Body Weight
Time frame: Day 1, 8 hours post-dose (end of infusion)

Results and safety

Results posted to the registry on 26 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence 1	12	12
Sequence 2	11	10

Primary outcome: 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. Mean (Standard Deviation). Unit: mL

Measure	BMS-986231 n = 21	Placebo n = 21
Sequence 1	900.7 (366.56)	1603.3 (674.18)
Sequence 2	1176.7 (386.21)	1345.4 (391.11)
Total	1032.1 (392.74)	1480.5 (559.92)

BMS-986231 vs Placebo: Mean Difference (Net): -448 (95% CI -714 to -183), p = 0.0021, t-test, 2 sided
BMS-986231 vs Placebo: Mean Difference (Net): -22.1 (95% CI -40.7 to -3.51), p = 0.0222, t-test, 2 sided

Population analysed: Treated (per Protocol set) - All randomized participants who were given both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each period.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose to 100 days post-last dose (up to ca. 4 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BMS-986231	1 of 23 (4.3%)	6 of 23 (26.1%)	0 of 23
Placebo	2 of 23 (8.7%)	3 of 23 (13%)	0 of 23

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31168885Felker 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.
BMS Clinical Trial InformationLink provided by the sponsor.
BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
FDA Safety Alerts and RecallsLink provided by the sponsor.

Related trials for Cardiac Failure

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BMS-986231 and Furosemide in people with Cardiac Failure and Myocardial Failure, run by Bristol-Myers Squibb at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03730961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.