Clinical trial NCT03016325: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-01-10
Enrollment: 329
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* 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%

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion
timeFrame: From start of infusion up to 6 hours post end of infusion
Secondary outcomes:
measure: Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32
timeFrame: 0, 24, 48, 72, 120 hour or discharge; Day 32
measure: Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72
timeFrame: Hours 6, 12, 24, 48, and 72
measure: Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion
timeFrame: From start of infusion up to 6 hours post end of infusion
measure: Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value)
timeFrame: From start of infusion up to 6 hours post end of infusion
measure: Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32
timeFrame: 32 days
measure: Number of Participants Who Discontinued Due to Hypotension
timeFrame: up to 120 hours (for AEs); up to 32 days (for SAEs)
measure: Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure
timeFrame: up to 120 hours (for AEs); up to 32 days (for SAEs)
measure: Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours
timeFrame: up to 120 hours
measure: Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182
timeFrame: through 182 days
measure: Change in Troponin T From Baseline to Hour 24, 48, and 72
timeFrame: from baseline to Hour 24, 48, and 72
measure: Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology
timeFrame: to 120 hours
measure: Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry
timeFrame: to 120 hours
measure: Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis
timeFrame: to 120 hours
measure: Change in Vital Signs From Baseline to 120 Hours - Blood Pressure
timeFrame: to 120 hours
measure: Change in Vital Signs From Baseline to 120 Hours - Heart Rate
timeFrame: to 120 hours
measure: Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate
timeFrame: to 120 hours
measure: Change in Vital Signs From Baseline to 120 Hours - Temperature
timeFrame: to 120 hours
measure: Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate
timeFrame: to 120 hours
measure: Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration
timeFrame: to 120 hours
measure: Change in Physical Measurements From Baseline to 120 Hours
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L)
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L)
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L)
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion
timeFrame: to 120 hours
measure: Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion
timeFrame: to 120 hours
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Sarver Heart Center
state: Arizona
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health Methodist Hospital
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Detroit
country: United States
facility: DMC Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Sinai Grace Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Wexner Medical Center at The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Caba
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Rosario
country: Argentina
facility: Local Institution
state: Santa FE
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Corrientes
country: Argentina
facility: Local Institution
city: Santa Fe
country: Argentina
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Halifax
country: Canada
facility: Local Institution
state: Nova Scotia
city: Quebec
country: Canada
facility: Local Institution
city: Brno
country: Czechia
facility: Local Institution
city: Brno
country: Czechia
facility: Local Institution
city: Hradec Kralove
country: Czechia
facility: Local Institution
city: Plzen-Bory
country: Czechia
facility: Local Institution
city: Prague
country: Czechia
facility: Local Institution
city: Praha 4
country: Czechia
facility: Local Institution
city: Slany
country: Czechia
facility: Local Institution
city: Besancon
country: France
facility: Local Institution
city: Beziers
country: France
facility: Local Institution
city: Bobigny
country: France
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Evreux
country: France
facility: Local Institution
city: La Tronche
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Bad Nauheim
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Gottingen
country: Germany
facility: Local Institution
city: Greifswald
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Homburg
country: Germany
facility: Local Institution
city: Ludwigshafen
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Regensburg
country: Germany
facility: Local Institution
city: Athens, Attiki
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Ioannina
country: Greece
facility: Local Institution
city: Kallithea
country: Greece
facility: Local Institution
city: Larisa
country: Greece
facility: Local Institution
city: Thessaloniki
country: Greece
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Ferrara
country: Italy
facility: Local Institution
city: Foggia
country: Italy
facility: Local Institution
city: Nagoya-shi
country: Japan
facility: Local Institution
state: Aichi
city: Seto
country: Japan
facility: Local Institution
state: Aichi
city: Fukushima-shi
country: Japan
facility: Local Institution
state: Fukushima
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Amagasaki
country: Japan
facility: Local Institution
state: Hyogo
city: Sagamihara-shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Okayama-shi
country: Japan
facility: Local Institution
state: Okayama
city: Suita-shi
country: Japan
facility: Local Institution
state: Osaka
city: Kawaguchi
country: Japan
facility: Local Institution
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Osaka
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Tokyo
country: Japan
facility: Local Institution
city: Amersfoort
country: Netherlands
facility: Local Institution
city: Deventer
country: Netherlands
facility: Local Institution
city: Hardenberg
country: Netherlands
facility: Local Institution
city: Leeuwarden
country: Netherlands
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Zamosc
country: Poland
facility: Local Institution
city: Alicante
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: L'Hospitalet de Llobregat
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Sant Joan Despi
country: Spain
facility: Local Institution
city: Santiago De Compostela
country: Spain
facility: Local Institution
city: Belfast
country: United Kingdom
facility: Local Institution
city: Blackpool
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.