Heart FailurePhase 2NCT03357731

A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function

A Phase 2 study testing HNO Donor and Nitroglycerin (NTG) in people with Heart Failure and Cardiac Failure, run by Bristol-Myers Squibb at 18 sites in 4 countries.

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 evaluate the effects of BMS-986231 on systolic and diastolic parameters in patients with heart failure and low ejection fraction. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure, Cardiac Failure, Reduced Ventricular Ejection Fraction
What is being tested?: HNO Donor and Nitroglycerin (NTG)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 18 sitesin 4 countries
Study dates: 30 Nov 2017to 10 May 2019
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

Heart failure with reduced ejection fraction (LVEF on echocardiogram of 40% or less)
Stable guideline directed therapy for heart failure including oral diuretics, ACEi, ARBs, ARNi, MRAs, and β blockers as tolerated, with no dose changes of these medications in the past 2 weeks
Have screening values of NT pro-BNP ≥ 125 pg/mL (15 pmol/L) or BNP ≥ 35 pg/mL (10 pmol/L)

Who cannot join

Systolic blood pressure (SBP) < 110 mm Hg at screening or pre-randomization
Heart rate < 50 beats per minute (bpm) or > 90 bpm at screening or pre-randomization
Permanent Atrial Fibrillation, Atrial Flutter or having Atrial Fibrillation, Atrial Flutter
Estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2
Ventricular assist device or prior heart transplant
Prior solid organ transplant

Show all 10Show fewer

Body weight < 45 kg or ≥ 140 kg
Low quality echocardiographic visualization windows and image acquisition
Permanent paced rhythm (VVI, DDD or BiV pacing)
Other protocol defined inclusion/exclusion criteria could apply

Trial locations and contacts

18 sites in 4 countries.

Country

City, postcode or hospital

18 sites in 4 countries

United Kingdom8 sites

Local Institution
Edinburgh, EH16 4SA
Local Institution
Glasgow, G4 0SF
Local Institution
Glasgow, G429LF
Local Institution
Glasgow, G51 4TF
Local Institution
Harrow, HA1 3UJ
Local Institution
London, SE1 1YR
Local Institution
London, sw17 0re
Local Institution
London, SW3 6NP

Other trials in United Kingdom

United States6 sites

Brigham and Womens Hospital
Boston, Massachusetts, 02115
Northwestern Medicine
Chicago, Illinois, 60611
Duke Advanced Heart and Lung Failure Clinic
Durham, North Carolina, 27710
Inova Heart and Vascular Institute
Falls Church, Virginia, 22042
Indiana University School of Medicine-Indianapolis
Indianapolis, Indiana, 46202-1218
Orange County Research Center
Tustin, California, 92780

Other trials in United States

Japan3 sites

Local Institution
Kawasaki, Kanagawa, 211-8533
Local Institution
Nagoya, Aichi-ken, 466-8560
Local Institution
Suita-shi, Osaka, 5650871

Other trials in Japan

Netherlands1 site

Local Institution
Groiningen, 9713GZ

Other trials in Netherlands

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Cross-over Phase 2 Study of Continuous 5-Hour Intravenous Infusions of BMS-986231 in Patients With Heart Failure and Impaired Systolic Function

The purpose of this study is to evaluate the effects of BMS-986231 on systolic and diastolic parameters in patients with heart failure and low ejection fraction.

Conditions: Heart Failure, Cardiac Failure, Reduced Ventricular Ejection Fraction
Being tested: HNO Donor, Nitroglycerin (NTG), 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.

HNO DonorDrug
Also called BMS-986231
Infusion
Nitroglycerin (NTG)Drug
Infusion
PlaceboOther
Infusion

Study groups in NCT03357731
Study group	Role	What they receive
Placebo/BMS-986231/NTG	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo
Placebo/NTG/BMS-986231	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo
NTG/Placebo/BMS-986231	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo
NTG/BMS-986231/Placebo	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo
BMS-986231/Placebo/NTG	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo
BMS-986231/NTG/Placebo	Experimental	administered in a cross over design with 5-hour infusions and 5-28 day wash-out periods Receives: Drug: HNO Donor; Drug: Nitroglycerin (NTG); Other: Placebo

What is being measured

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

Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo
The objective is to evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to placebo.
Measured: at the end of the 5-hour infusion

Secondary outcomes (6)

Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG
The objective is to evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to NTG.
Measured: at the end of the 5-hour infusion
Mean LVEF, Computed by Simpson's Method at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG:
LV ejection fraction
Measured: at the end of the 5-hour infusion
Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG:
Mean LV power index
Measured: at the end of the 5-hour infusion
Mean Diastolic Indices: E/A and E/e' Ratio at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG:
Diastolic function
Measured: at the end of the 5-hour infusion
Mean Diastolic Indices: Annular e' Velocity at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG:
Diastolic function
Measured: at the end of the 5-hour infusion
Mean LV Global Longitudinal Strain, Computed Using STE at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG:
LV global longitudinal strain
Measured: at the end of the 5-hour infusion

Timeline

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

30 Nov 201710 May 2019

First posted30 Nov 2017
Study start30 Nov 2017
Primary completion10 May 2019
Study completion10 May 2019

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 Heart 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: None (open label)
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03357731
Sponsor's protocol ID: CV013-020
Other IDs: 2016-003586-26, 2016
Status last verified: Jul 2020
First submitted: 31 Oct 2017
Last updated: 27 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
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 Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Cross-over Phase 2 Study of Continuous 5-Hour Intravenous Infusions of BMS-986231 in Patients With Heart Failure and Impaired Systolic Function
ClinicalTrials.gov ID: NCT03357731
Acronym / sponsor ID: CV013-020
Conditions: Heart Failure, Cardiac Failure, Reduced Ventricular Ejection Fraction
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: 30 Nov 2017 (actual)
Primary completion: 10 May 2019 (actual)
Study completion: 10 May 2019 (actual)
First posted: 30 Nov 2017 (actual)
Results: Posted 27 Jul 2020

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 evaluate the effects of BMS-986231 on systolic and diastolic parameters in patients with heart failure and low ejection fraction.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Placebo/BMS-986231/NTG	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
Placebo/NTG/BMS-986231	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/Placebo/BMS-986231	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
NTG/BMS-986231/Placebo	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/Placebo/NTG	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 day wash-out periods
BMS-986231/NTG/Placebo	Experimental	Drug: HNO Donor, Drug: Nitroglycerin (NTG), Other: Placeboadministered in a cross over design with 5-hour infusions and 5-28 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)

Heart failure with reduced ejection fraction (LVEF on echocardiogram of 40% or less)
Stable guideline directed therapy for heart failure including oral diuretics, ACEi, ARBs, ARNi, MRAs, and β blockers as tolerated, with no dose changes of these medications in the past 2 weeks
Have screening values of NT pro-BNP ≥ 125 pg/mL (15 pmol/L) or BNP ≥ 35 pg/mL (10 pmol/L)

Key exclusion criteria (10 listed)

Systolic blood pressure (SBP) < 110 mm Hg at screening or pre-randomization
Heart rate < 50 beats per minute (bpm) or > 90 bpm at screening or pre-randomization
Permanent Atrial Fibrillation, Atrial Flutter or having Atrial Fibrillation, Atrial Flutter
Estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2
Ventricular assist device or prior heart transplant

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
HNO DonorAlso: BMS-986231Infusion	Drug	BMS-986231/NTG/Placebo, BMS-986231/Placebo/NTG, NTG/BMS-986231/Placebo, NTG/Placebo/BMS-986231, Placebo/BMS-986231/NTG, Placebo/NTG/BMS-986231
Nitroglycerin (NTG)Infusion	Drug	BMS-986231/NTG/Placebo, BMS-986231/Placebo/NTG, NTG/BMS-986231/Placebo, NTG/Placebo/BMS-986231, Placebo/BMS-986231/NTG, Placebo/NTG/BMS-986231
PlaceboInfusion	Other	BMS-986231/NTG/Placebo, BMS-986231/Placebo/NTG, NTG/BMS-986231/Placebo, NTG/Placebo/BMS-986231, Placebo/BMS-986231/NTG, Placebo/NTG/BMS-986231

Primary outcome

Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo
Time frame: at the end of the 5-hour infusion
The objective is to evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to placebo.

6 secondary outcomes

Mean SVI Derived From LVOT VTI at the End of the 5-hour Infusion of BMS-986231, Versus NTG
Time frame: at the end of the 5-hour infusion
Mean LVEF, Computed by Simpson's Method at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Time frame: at the end of the 5-hour infusion
Mean Cardiac Power Index at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Time frame: at the end of the 5-hour infusion
Mean Diastolic Indices: E/A and E/e' Ratio at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Time frame: at the end of the 5-hour infusion
Mean Diastolic Indices: Annular e' Velocity at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Time frame: at the end of the 5-hour infusion
Mean LV Global Longitudinal Strain, Computed Using STE at the End of the 5-hour Infusion of BMS-986231, Versus Placebo and NTG
Time frame: at the end of the 5-hour infusion

Results and safety

Results posted to the registry on 27 Jul 2020, 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	8	8
Sequence 2	7	7
Sequence 3	7	6
Sequence 4	7	4
Sequence 5	8	7
Sequence 6	8	7

Primary outcome: Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo

Time frame: at the end of the 5-hour infusion. Mean (Standard Deviation). Unit: mL/m^2

Measure	Placebo (PBO) n = 39	BMS-986231 n = 37	Nitroglycerin (NTG) n = 0
Value	29.545 (7.0243)	28.721 (9.0174)	–

Placebo (PBO) vs BMS-986231: Mean Difference (Net): -2.150 (95% CI -4.0432 to -0.2570), p = 0.027, Kenward-Roger degree of freedom

Population analysed: Intent to Treat (ITT) population: All randomized participants who started study drug infusion in at least one treatment period.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose to 30 days post last dose (approximately 3 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo (PBO)	1 of 40 (2.5%)	2 of 40 (5%)	0 of 40
BMS-986231	0 of 42 (0%)	12 of 42 (28.6%)	0 of 42
Nitroglycerin (NTG)	1 of 44 (2.3%)	10 of 44 (22.7%)	0 of 44

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
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 Heart 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
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Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
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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.

The record lists no contact. Use the official record to reach the sponsor.

18 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HNO Donor and Nitroglycerin (NTG) in people with Heart Failure and Cardiac Failure, run by Bristol-Myers Squibb at 18 sites in 4 countries.

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 10 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 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United Kingdom, United States, Japan, Netherlands. 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 27 Jul 2020). 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?

Mean Stroke Volume Index (SVI) Derived From the Velocity Time Integral at the Left Ventricular Outflow Tract (LVOT VTI) at the End of the 5-hour Infusion of BMS-986231, Versus Placebo (time frame: at the end of the 5-hour infusion). 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 NCT03357731, 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 27 Jul 2020.