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

NCT03016325 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CV013-0112016-001685-29
• Study Type: interventional
• Target: 329
• Locations: 13 countries
• Sites: 116

Brief 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

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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

  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

  0, 24, 48, 72, 120 hour or discharge; Day 32

• Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72

  Hours 6, 12, 24, 48, and 72

• Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion

  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)

  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

  32 days

Study Arms (5)

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

Interventions

HNO Donor DRUG

Infusion

Also known as: BMS-986231

Part 1 Cohort 1 HNO Donor; Part 2 Cohort 2 HNO Donor- high dose; Part 2 Cohort 2 HNO Donor- low dose

Placebo DRUG

Infusion

Placebo Part 1 Cohort 1; Placebo Part 2 Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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%

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (116)

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

DMC Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

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Harper University Hospital

Detroit, Michigan, 48201, United States

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Henry Ford Health System

Detroit, Michigan, 48202, United States

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Sinai Grace Hospital

Detroit, Michigan, 48235, United States

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Saint Louis University

St Louis, Missouri, 63110, United States

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Washington University

St Louis, Missouri, 63110, United States

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

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University of Cincinnati

Cincinnati, Ohio, 45267, United States

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Wexner Medical Center at The Ohio State University

Columbus, Ohio, 43210, United States

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University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

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Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

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Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425, United States

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Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

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University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

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Ben Taub General Hospital

Houston, Texas, 77030, United States

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University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

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University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Local Institution

CABA, Buenos Aires, C1428ART, Argentina

Location

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Rosario, Santa Fe Province, Santa Fe, 2000, Argentina

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Buenos Aires, Argentina

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Corrientes, 3400, Argentina

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Córdoba, 5000, Argentina

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Córdoba, X5000AAX, Argentina

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Córdoba, X5000EPU, Argentina

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Córdoba, X5000JHQ, Argentina

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Córdoba, Argentina

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Santa Fe, 3000, Argentina

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Edmonton, Alberta, T6G 2R3, Canada

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Halifax, Nova Scotia, B3H 4S9, Canada

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Québec, Quebec, G1V 4G5, Canada

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Brno, 625 00, Czechia

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Brno, 656 91, Czechia

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Hradec Králové, 500 05, Czechia

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Plzen-Bory, 305 99, Czechia

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Prague, 12808, Czechia

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Prague, 140 21, Czechia

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Slaný, 274 01, Czechia

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Besançon, 25000, France

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Béziers, 34500, France

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Bobigny, 93009, France

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Créteil, France

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Évreux, 27015, France

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La Tronche, 38700, France

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Paris, 75013, France

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Paris, 75475, France

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Bad Nauheim, 61231, Germany

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Frankfurt, 60590, Germany

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Göttingen, 37075, Germany

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Greifswald, Germany

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Hamburg, 20246, Germany

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Hanover, 30625, Germany

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Homburg, 66421, Germany

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Ludwigshafen, 67063, Germany

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Mainz, Germany

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Regensburg, 935053, Germany

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Athens, 11527, Greece

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Athens, 12464, Greece

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Athens, 14233, Greece

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Athens, Attiki, 11527, Greece

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Ioannina, 45500, Greece

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Kallithea, 17674, Greece

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Larissa, 41110, Greece

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Thessaloniki, 54636, Greece

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Brescia, 25123, Italy

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Ferrara, 44121, Italy

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Foggia, 71121, Italy

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Nagoya, Aichi-ken, 4678602, Japan

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Seto, Aichi-ken, 489-0065, Japan

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Fukushima, Fukushima, 9601295, Japan

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Sapporo, Hokkaido, 0608648, Japan

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Amagasaki, Hyōgo, 6608550, Japan

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Sagamihara-shi, Kanagawa, 2520375, Japan

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Yokohama, Kanagawa, 227-8501, Japan

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Yokohama, Kanagawa, 232-0024, Japan

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Okayama, Okayama-ken, 7008558, Japan

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Suita-shi, Osaka, Japan

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Kawaguchi, Saitama, 333-0842, Japan

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Bunkyo-ku, Tokyo, 1138431, Japan

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Bunkyo-ku, Tokyo, 1138603, Japan

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Itabashi-ku, Tokyo, 1738610, Japan

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Osaka, 558-8558, Japan

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Tokyo, 113-8655, Japan

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Tokyo, 162-8655, Japan

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Amersfoort, 3818 ES, Netherlands

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Deventer, 7416 SE, Netherlands

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Hardenberg, 7772 SE, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Bialystok, 15-276, Poland

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Katowice, 40-635, Poland

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Krakow, 31-202, Poland

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Lodz, 91-347, Poland

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Lodz, 92-213, Poland

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Warsaw, 04-628, Poland

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Wroclaw, 50-981, Poland

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Wroclaw, 54-049, Poland

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Zamość, 22-400, Poland

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Alicante, 03010, Spain

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Barcelona, 08025, Spain

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Barcelona, 8035, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 28007, Spain

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Madrid, 28041, Spain

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Sant Joan Despí, 08970, Spain

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Santiago de Compostela, 15706, Spain

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Belfast, BT16 1RH, United Kingdom

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Blackpool, FY3 8NR, United Kingdom

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Glasgow, G4 0SF, United Kingdom

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Glasgow, G51 4TF, United Kingdom

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London, SW17 0QT, United Kingdom

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Related Publications (2)

• 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.

  PMID: 33248986 DERIVED

• 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.

  PMID: 30703258 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

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 10, 2017
• Study Start: January 13, 2017
• Primary Completion: June 23, 2019
• Study Completion: November 12, 2019
• Last Updated: January 6, 2021
• Results First Posted: August 19, 2020

Record last verified: 2020-12

Locations

FR (8); PL (9); US (24); GR (8); DE (10); IT (3); JP (17); ES (8); GB (5); NL (4); CA (3); AR (10); CZ (7)