Heart FailurePhase 2STANDUP AHFNCT03016325

Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure

A Phase 2 study testing HNO Donor in people with Heart Failure, run by Bristol-Myers Squibb at 116 sites in 13 countries.

Completed

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

Official record

Search all trials

Trial summary

A Study to Evaluate Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of HNO Donor in Hospitalized Patients with Heart Failure and Impaired Systolic Function Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure
What is being tested?: HNO Donor
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 329 participants
Where: 116 sitesin 13 countries
Study dates: 13 Jan 2017to 12 Nov 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

Actively being hospitalized for acute decompensated heart failure
At least 1 administration of IV diuretic for the current episode
Be randomized within 18 hours of first dose of IV diuretic for current episode for Part 1 Cohort 1, or 48 hours for first dose for Part II Cohort II
Have shortness of breath at rest or with minimal exertion after administration of 1 dose of IV diuretic
Have history of heart failure and a left ventricular ejection fraction (LVEF) ≤ 40%

Who cannot join

Systolic blood pressure <105mm Hg or >160mm Hg or heart rate <50 or >130 bpm
Have an active infection requiring IV anti-microbial treatment
Be hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening
Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening
Suspected acute lung disease (e.g pneumonia or asthma) or severe chronic lung disease (e.g. severe chronic obstructive pulmonary disease, or pulmonary fibrosis)
Other protocol defined inclusion/exclusion criteria could apply

Trial locations and contacts

116 sites in 13 countries.

Country

City, postcode or hospital

116 sites in 13 countries

United States24 sites

Emory University
Atlanta, Georgia, 30322
University of Maryland Medical Center
Baltimore, Maryland, 21201
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina - PPDS
Charleston, South Carolina, 29425
University of Virginia Health System
Charlottesville, Virginia, 22908
University of Cincinnati
Cincinnati, Ohio, 45267
Wexner Medical Center at The Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
DMC Detroit Receiving Hospital
Detroit, Michigan, 48201
Harper University Hospital
Detroit, Michigan, 48201
Henry Ford Health System
Detroit, Michigan, 48202
Sinai Grace Hospital
Detroit, Michigan, 48235
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
Ben Taub General Hospital
Houston, Texas, 77030
Indiana University Health Methodist Hospital
Indianapolis, Indiana, 46202
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of Utah Medical Center
Salt Lake City, Utah, 84132
Saint Louis University
St Louis, Missouri, 63110
Washington University
St Louis, Missouri, 63110
Tampa General Hospital
Tampa, Florida, 33606
University of Arizona Sarver Heart Center
Tucson, Arizona, 85724

Other trials in United States

Japan17 sites

Local Institution
Amagasaki, Hyōgo, 6608550
Local Institution
Bunkyo-ku, Tokyo, 1138431
Local Institution
Bunkyo-ku, Tokyo, 1138603
Local Institution
Fukushima, Fukushima, 9601295
Local Institution
Kawaguchi, Saitama, 333-0842
Local Institution
Nagoya, Aichi-ken, 4678602
Local Institution
Okayama, Okayama-ken, 7008558
Local Institution
Osaka, 558-8558
Local Institution
Sagamihara-shi, Kanagawa, 2520375
Local Institution
Sapporo, Hokkaido, 0608648
Local Institution
Seto, Aichi-ken, 489-0065
Local Institution
Suita-shi, Osaka
Local Institution
tabashi City, Tokyo, 1738610
Local Institution
Tokyo, 113-8655
Local Institution
Tokyo, 162-8655
Local Institution
Yokohama, Kanagawa, 227-8501
Local Institution
Yokohama, Kanagawa, 232-0024

Other trials in Japan

Argentina10 sites

Local Institution
Buenos Aires
Local Institution
CABA, Buenos Aires, C1428ART
Local Institution
Córdoba, 5000
Local Institution
Córdoba, X5000AAX
Local Institution
Córdoba, X5000EPU
Local Institution
Córdoba, X5000JHQ
Local Institution
Córdoba
Local Institution
Corrientes, 3400
Local Institution
Rosario, Santa Fe Province, Santa Fe, 2000
Local Institution
Santa Fe, 3000

Other trials in Argentina

Germany10 sites

Local Institution
Bad Nauheim, 61231
Local Institution
Frankfurt, 60590
Local Institution
Göttingen, 37075
Local Institution
Greifswald
Local Institution
Hamburg, 20246
Local Institution
Hanover, 30625
Local Institution
Homburg, 66421
Local Institution
Ludwigshafen, 67063
Local Institution
Mainz
Local Institution
Regensburg, 935053

Other trials in Germany

Poland9 sites

Local Institution
Bialystok, 15-276
Local Institution
Katowice, 40-635
Local Institution
Krakow, 31-202
Local Institution
Lodz, 91-347
Local Institution
Lodz, 92-213
Local Institution
Warsaw, 04-628
Local Institution
Wroclaw, 50-981
Local Institution
Wroclaw, 54-049
Local Institution
Zamość, 22-400

Other trials in Poland

France8 sites

Local Institution
Besançon, 25000
Local Institution
Béziers, 34500
Local Institution
Bobigny, 93009
Local Institution
Créteil
Local Institution
Évreux, 27015
Local Institution
La Tronche, 38700
Local Institution
Paris, 75013
Local Institution
Paris, 75475

Other trials in France

Greece8 sites

Local Institution
Athens, 11527
Local Institution
Athens, 12464
Local Institution
Athens, 14233
Local Institution
Athens, Attiki, 11527
Local Institution
Ioannina, 45500
Local Institution
Kallithea, 17674
Local Institution
Larissa, 41110
Local Institution
Thessaloniki, 54636

Other trials in Greece

Spain8 sites

Local Institution
Alicante, 03010
Local Institution
Barcelona, 08025
Local Institution
Barcelona, 8035
Local Institution
L'Hospitalet de Llobregat, 08907
Local Institution
Madrid, 28007
Local Institution
Madrid, 28041
Local Institution
Sant Joan Despí, 08970
Local Institution
Santiago de Compostela, 15706

Other trials in Spain

Czechia7 sites

Local Institution
Brno, 625 00
Local Institution
Brno, 656 91
Local Institution
Hradec Králové, 500 05
Local Institution
Plzen-Bory, 305 99
Local Institution
Prague, 12808
Local Institution
Prague, 140 21
Local Institution
Slaný, 274 01

Other trials in Czechia

United Kingdom5 sites

Local Institution
Belfast, BT16 1RH
Local Institution
Blackpool, FY3 8NR
Local Institution
Glasgow, G4 0SF
Local Institution
Glasgow, G51 4TF
Local Institution
London, SW17 0QT

Other trials in United Kingdom

Netherlands4 sites

Local Institution
Amersfoort, 3818 ES
Local Institution
Deventer, 7416 SE
Local Institution
Hardenberg, 7772 SE
Local Institution
Leeuwarden, 8934 AD

Other trials in Netherlands

Canada3 sites

Local Institution
Edmonton, Alberta, T6G 2R3
Local Institution
Halifax, Nova Scotia, B3H 4S9
Local Institution
Québec, Quebec, G1V 4G5

Other trials in Canada

Italy3 sites

Local Institution
Brescia, 25123
Local Institution
Ferrara, 44121
Local Institution
Foggia, 71121

Other trials in Italy

About this study

Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose-Ranging, Phase 2b Study of the Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of BMS-986231 in Hospitalized Patients With Heart Failure and Impaired Systolic Function

A Study to Evaluate Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of HNO Donor in Hospitalized Patients with Heart Failure and Impaired Systolic Function

Conditions: Heart Failure
Being tested: HNO Donor, 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
PlaceboDrug
Infusion

Study groups in NCT03016325
Study group	Role	What they receive
Part 1 Cohort 1 HNO Donor	Experimental	Not described Receives: Drug: HNO Donor
Placebo Part 1 Cohort 1	Placebo comparator	Not described Receives: Drug: Placebo
Part 2 Cohort 2 HNO Donor- low dose	Experimental	Not described Receives: Drug: HNO Donor
Part 2 Cohort 2 HNO Donor- high dose	Experimental	Not described Receives: Drug: HNO Donor
Placebo Part 2 Cohort 2	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

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

Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion
Percentage of participants with clinically relevant hypotension, defined by systolic blood pressure (SBP) < 90 mm Hg (confirmed by a repeated value < 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion
Measured: From start of infusion up to 6 hours post end of infusion

Secondary outcomes (31)

Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32
Assess the effect of BMS-986231 on NT-proBNP (N-terminal prohormone of brain natriuretic peptide)
Measured: 0, 24, 48, 72, 120 hour or discharge; Day 32
Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72
Endpoint was measured by the area under the curve (AUC) of the 11-point Numerical Rating Scale (NRS) obtained at baseline, and Hours 6, 12, 24, 48, and 72.
Participants were asked to report their absolute current severity of dyspnea on an 11-point numerical rating scale (NRS; range 0 to 10).
The numerical rating scale (NRS) was used to assess the degree of dyspnea (breathlessness), measured using an 11-point scale provided by the Sponsor.
A score of 0 represents "I am not breathless at all" and 10 represents "I am the most breathless I can possibly imagine".
Measured: Hours 6, 12, 24, 48, and 72
Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion
The percentage of participants experiencing symptoms of hypotension up to 6 hours post-treatment was reported for each arm.
Measured: From start of infusion up to 6 hours post end of infusion
Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value)
The percentage of participants experiencing SBP < 90 mm Hg (confirmed by a repeated value) up to 6 hours post-treatment was reported for each arm.
Measured: From start of infusion up to 6 hours post end of infusion
Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32
Number of participants who experienced an in-study SAE.
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment.
Measured: 32 days
Number of Participants Who Discontinued Due to Hypotension
Number of participants who discontinued study treatment due to hypotension.
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment.
Hypotension defined as systolic blood pressure (SBP) < 90 mmHg.
Measured: up to 120 hours (for AEs); up to 32 days (for SAEs)
Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure
Number of participants who discontinued study treatment, experienced a down-titration (dose reduction) or dose interruption due to decreased blood pressure/hypotension are reported below.
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment.
If the participant experienced systolic blood pressure (SBP) < 95 mm Hg, without symptoms related to hypotension, the measurement was repeated within 15 minutes. If the SBP remained < 95 mm Hg, the dose reduction occurred.
Measured: up to 120 hours (for AEs); up to 32 days (for SAEs)
Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours
Number of participants who experienced an in-study AE.
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment.
Measured: up to 120 hours
Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182
Number of participants who died (all- cause and CV related) through Day 182.
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
CV=Cardiovascular
Measured: through 182 days
Change in Troponin T From Baseline to Hour 24, 48, and 72
Baseline = Last non-missing result with a collection date-time less than or on the date-time of the start of infusion of study drug
Measured: from baseline to Hour 24, 48, and 72
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology
Number of participants who experienced an in-study Hematology marked laboratory abnormality (reported in > 5% of total participants).
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Measured: to 120 hours
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry
Number of participants who experienced an in-study Chemistry marked laboratory abnormality (reported in > 5% of total participants).
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Measured: to 120 hours
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis
Number of participants who experienced an in-study Urinalysis marked laboratory abnormality (reported in > 5% of total participants).
Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Measured: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Blood Pressure
The change in baseline for vital signs was reported for each arm.
Measured: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Heart Rate
The change in baseline for vital signs was reported for each arm.
Measured: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate
The change in baseline for vital signs was reported for each arm.
Measured: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Temperature
The change in baseline for vital signs was reported for each arm.
Measured: to 120 hours
Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate
The change in baseline for ECGs was reported for each arm.
Measured: to 120 hours
Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration
The change in baseline for ECGs was reported for each arm.
Measured: to 120 hours
Change in Physical Measurements From Baseline to 120 Hours
The change in baseline for physical measurements was reported for each arm.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L
The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L)
The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L)
The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L)
The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion
The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Measured: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion
The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Measured: to 120 hours

Timeline

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

13 Jan 201712 Nov 2019

First posted10 Jan 2017 (estimated)
Study start13 Jan 2017
Primary completion23 Jun 2019
Study completion12 Nov 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 (2)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: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 329 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03016325
Sponsor's protocol ID: CV013-011
Other IDs: 2016-001685-29, 2016
Acronym: STANDUP AHF
Status last verified: Dec 2020
First submitted: 9 Jan 2017
Last updated: 6 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Felker GM, McMurray JJV, Cleland JG, O'Connor CM, Teerlink JR, Voors AA, Belohlavek J, Bohm M, Borentain M, Bueno H, Cole RT, DeSouza MM, Ezekowitz JA, Filippatos G, Lang NN, Kessler PD, Martinez FA, Mebazaa A, Metra M, Mosterd A, Pang PS, Ponikowski P, Sato N, Seiffert D, Ye J. Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. JACC Heart Fail. 2021 Feb;9(2):146-157. doi: 10.1016/j.jchf.2020.10.012. Epub 2020 Nov 25.
PubMed 33248986
Cowart D, Venuti RP, Lynch K, Guptill JT, Noveck RJ, Foo SY. A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers. J Clin Pharmacol. 2019 May;59(5):717-730. doi: 10.1002/jcph.1364. Epub 2019 Jan 31.
PubMed 30703258

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

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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 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose-Ranging, Phase 2b Study of the Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of BMS-986231 in Hospitalized Patients With Heart Failure and Impaired Systolic Function
ClinicalTrials.gov ID: NCT03016325
Acronym / sponsor ID: STANDUP AHF / CV013-011
Conditions: Heart Failure
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 329 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Study start: 13 Jan 2017 (actual)
Primary completion: 23 Jun 2019 (actual)
Study completion: 12 Nov 2019 (actual)
First posted: 10 Jan 2017 (estimated)
Results: Posted 19 Aug 2020

Clinical summary

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

A Study to Evaluate Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of HNO Donor in Hospitalized Patients with Heart Failure and Impaired Systolic Function

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Part 1 Cohort 1 HNO Donor	Experimental	Drug: HNO Donor
Placebo Part 1 Cohort 1	Placebo comparator	Drug: Placebo
Part 2 Cohort 2 HNO Donor- low dose	Experimental	Drug: HNO Donor
Part 2 Cohort 2 HNO Donor- high dose	Experimental	Drug: HNO Donor
Placebo Part 2 Cohort 2	Placebo comparator	Drug: Placebo

Who may qualify

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

Key inclusion criteria (5 listed)

Actively being hospitalized for acute decompensated heart failure
At least 1 administration of IV diuretic for the current episode
Be randomized within 18 hours of first dose of IV diuretic for current episode for Part 1 Cohort 1, or 48 hours for first dose for Part II Cohort II
Have shortness of breath at rest or with minimal exertion after administration of 1 dose of IV diuretic
Have history of heart failure and a left ventricular ejection fraction (LVEF) ≤ 40%

Key exclusion criteria (6 listed)

Systolic blood pressure <105mm Hg or >160mm Hg or heart rate <50 or >130 bpm
Have an active infection requiring IV anti-microbial treatment
Be hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening
Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening
Suspected acute lung disease (e.g pneumonia or asthma) or severe chronic lung disease (e.g. severe chronic obstructive pulmonary disease, or pulmonary fibrosis)

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	Part 1 Cohort 1 HNO Donor, Part 2 Cohort 2 HNO Donor- high dose, Part 2 Cohort 2 HNO Donor- low dose
PlaceboInfusion	Drug	Placebo Part 1 Cohort 1, Placebo Part 2 Cohort 2

Primary outcome

Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion
Time frame: From start of infusion up to 6 hours post end of infusion
Percentage of participants with clinically relevant hypotension, defined by systolic blood pressure (SBP) < 90 mm Hg (confirmed by a repeated value < 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion

31 secondary outcomes

Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32
Time frame: 0, 24, 48, 72, 120 hour or discharge; Day 32
Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72
Time frame: Hours 6, 12, 24, 48, and 72
Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion
Time frame: From start of infusion up to 6 hours post end of infusion
Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value)
Time frame: From start of infusion up to 6 hours post end of infusion
Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32
Time frame: 32 days
Number of Participants Who Discontinued Due to Hypotension
Time frame: up to 120 hours (for AEs); up to 32 days (for SAEs)
Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure
Time frame: up to 120 hours (for AEs); up to 32 days (for SAEs)
Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours
Time frame: up to 120 hours
Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182
Time frame: through 182 days
Change in Troponin T From Baseline to Hour 24, 48, and 72
Time frame: from baseline to Hour 24, 48, and 72
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology
Time frame: to 120 hours
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry
Time frame: to 120 hours
Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis
Time frame: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Blood Pressure
Time frame: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Heart Rate
Time frame: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate
Time frame: to 120 hours
Change in Vital Signs From Baseline to 120 Hours - Temperature
Time frame: to 120 hours
Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate
Time frame: to 120 hours
Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration
Time frame: to 120 hours
Change in Physical Measurements From Baseline to 120 Hours
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L)
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L)
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L)
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion
Time frame: to 120 hours
Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion
Time frame: to 120 hours

Results and safety

Results posted to the registry on 19 Aug 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
Placebo - Part I	48	48
BMS-986231 - Part I	49	48
Placebo - Part II	71	70
BMS-986231 6 µg/kg/Min - Part II	71	71
BMS-986231 12 µg/kg/Min - Part II	72	70
Placebo - Part II (Japan Cohort)	6	6
BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	6	6
BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)	6	6

Primary outcome: Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion

Time frame: From start of infusion up to 6 hours post end of infusion. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Placebo - Part I n = 48	BMS-986231 - Part I n = 49	Placebo - Part II n = 71	BMS-986231 6 µg/kg/Min - Part II n = 71	BMS-986231 12 µg/kg/Min - Part II n = 72	Placebo - Part II (Japan Cohort) n = 6	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort) n = 6	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort) n = 6
clinically relevant hypotension	8.3 (2.32 to 19.98)	20.4 (10.24 to 34.34)	18.3 (10.13 to 29.27)	21.1 (12.33 to 32.44)	34.7 (23.88 to 46.86)	0 (0.00 to 45.93)	33.3 (4.33 to 77.72)	50.0 (11.81 to 88.19)
symptoms of hypotension	2.1 (0.05 to 11.07)	6.1 (1.28 to 16.87)	1.4 (0.04 to 7.60)	2.8 (0.34 to 9.81)	8.3 (3.12 to 17.26)	0 (0.00 to 45.93)	0 (0.00 to 45.93)	0 (0.00 to 45.93)
confirmed SBP < 90 mmHg	6.3 (1.31 to 17.20)	20.4 (10.24 to 34.34)	18.3 (10.13 to 29.27)	21.1 (12.33 to 32.44)	29.2 (19.05 to 41.07)	0 (0.00 to 45.93)	33.3 (4.33 to 77.72)	50.0 (11.81 to 88.19)

Placebo - Part I vs BMS-986231 - Part I: Relative risk from placebo: 2.45 (95% CI 0.83 to 14.53)
Placebo - Part I vs BMS-986231 - Part I: Relative difference from placebo: 0.12 (95% CI -0.02 to 0.28)
Placebo - Part I vs BMS-986231 - Part I: Relative risk from placebo: 2.94 (95% CI 0.31 to 75.47)

Population analysed: All treated participants

31 secondary outcomes are reported in the full results.

Adverse events

Time frame: Includes non-serious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. Mortality data reported through 182 days post-treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo - Part I	11 of 48 (22.9%)	18 of 48 (37.5%)	3 of 48
BMS-986231 - Part I	14 of 49 (28.6%)	40 of 49 (81.6%)	3 of 49
Placebo - Part II	23 of 71 (32.4%)	47 of 71 (66.2%)	11 of 71
BMS-986231 6 µg/kg/Min - Part II	15 of 71 (21.1%)	43 of 71 (60.6%)	12 of 71
BMS-986231 12 µg/kg/Min - Part II	15 of 72 (20.8%)	54 of 72 (75%)	9 of 72
Placebo - Part II (Japan Cohort)	1 of 6 (16.7%)	2 of 6 (33.3%)	0 of 6
BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)	1 of 6 (16.7%)	6 of 6 (100%)	1 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33248986Felker GM, McMurray JJV, Cleland JG, O'Connor CM, Teerlink JR, Voors AA, Belohlavek J, Bohm M, Borentain M, Bueno H, Cole RT, DeSouza MM, Ezekowitz JA, Filippatos G, Lang NN, Kessler PD, Martinez FA, Mebazaa A, Metra M, Mosterd A, Pang PS, Ponikowski P, Sato N, Seiffert D, Ye J. Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. JACC Heart Fail. 2021 Feb;9(2):146-157. doi: 10.1016/j.jchf.2020.10.012. Epub 2020 Nov 25.
Derived from this study: PubMed 30703258Cowart D, Venuti RP, Lynch K, Guptill JT, Noveck RJ, Foo SY. A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers. J Clin Pharmacol. 2019 May;59(5):717-730. doi: 10.1002/jcph.1364. Epub 2019 Jan 31.
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.

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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.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

116 sites in 13 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HNO Donor in people with Heart Failure, run by Bristol-Myers Squibb at 116 sites in 13 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 5 inclusion and 6 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 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 116 sites in United States, Japan, Argentina, Germany, Poland and 8 more countries. 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. Some participants in this study may receive a placebo. 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 19 Aug 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?

Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion (time frame: From start of infusion up to 6 hours post end of 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 NCT03016325, which also lists 2 linked publications.

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 6 Jan 2021.