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

Heart Failure Clinical Trial

— STANDUP AHF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03016325
• Other study ID #: CV013-011
• Secondary ID: 2016-001685-29
• Status: Completed
• Phase: Phase 2
• Start date: January 13, 2017
• Est. completion date: November 12, 2019

Study information

• Verified date: December 2020
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 329
• Est. completion date: November 12, 2019
• Est. primary completion date: June 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• HNO Donor
Infusion
• Placebo
Infusion

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Caba	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Corrientes
Argentina	Local Institution	Rosario	Santa FE
Argentina	Local Institution	Santa Fe
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Halifax	Nova Scotia
Canada	Local Institution	Quebec
Czechia	Local Institution	Brno
Czechia	Local Institution	Brno
Czechia	Local Institution	Hradec Kralove
Czechia	Local Institution	Plzen-Bory
Czechia	Local Institution	Prague
Czechia	Local Institution	Praha 4
Czechia	Local Institution	Slany
France	Local Institution	Besancon
France	Local Institution	Beziers
France	Local Institution	Bobigny
France	Local Institution	Creteil
France	Local Institution	Evreux
France	Local Institution	La Tronche
France	Local Institution	Paris
France	Local Institution	Paris Cedex 10
Germany	Local Institution	Bad Nauheim
Germany	Local Institution	Frankfurt
Germany	Local Institution	Gottingen
Germany	Local Institution	Greifswald
Germany	Local Institution	Hamburg
Germany	Local Institution	Hannover
Germany	Local Institution	Homburg
Germany	Local Institution	Ludwigshafen
Germany	Local Institution	Mainz
Germany	Local Institution	Regensburg
Greece	Local Institution	Athens
Greece	Local Institution	Athens
Greece	Local Institution	Athens
Greece	Local Institution	Athens, Attiki
Greece	Local Institution	Ioannina
Greece	Local Institution	Kallithea
Greece	Local Institution	Larisa
Greece	Local Institution	Thessaloniki
Italy	Local Institution	Brescia
Italy	Local Institution	Ferrara
Italy	Local Institution	Foggia
Japan	Local Institution	Amagasaki	Hyogo
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Bunkyo-ku	Tokyo
Japan	Local Institution	Fukushima-shi	Fukushima
Japan	Local Institution	Itabashi-ku	Tokyo
Japan	Local Institution	Kawaguchi	Saitama
Japan	Local Institution	Nagoya-shi	Aichi
Japan	Local Institution	Okayama-shi	Okayama
Japan	Local Institution	Osaka
Japan	Local Institution	Sagamihara-shi	Kanagawa
Japan	Local Institution	Sapporo-shi	Hokkaido
Japan	Local Institution	Seto	Aichi
Japan	Local Institution	Suita-shi	Osaka
Japan	Local Institution	Tokyo
Japan	Local Institution	Tokyo
Japan	Local Institution	Yokohama	Kanagawa
Japan	Local Institution	Yokohama	Kanagawa
Netherlands	Local Institution	Amersfoort
Netherlands	Local Institution	Deventer
Netherlands	Local Institution	Hardenberg
Netherlands	Local Institution	Leeuwarden
Poland	Local Institution	Bialystok
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lodz
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Poland	Local Institution	Wroclaw
Poland	Local Institution	Zamosc
Spain	Local Institution	Alicante
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	L'Hospitalet de Llobregat
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Sant Joan Despi
Spain	Local Institution	Santiago De Compostela
United Kingdom	Local Institution	Belfast
United Kingdom	Local Institution	Blackpool
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	London
United States	Emory University	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina - PPDS	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Cincinnati	Cincinnati	Ohio
United States	Wexner Medical Center at The Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	DMC Detroit Receiving Hospital	Detroit	Michigan
United States	Harper University Hospital	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	Sinai Grace Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Ben Taub General Hospital	Houston	Texas
United States	Indiana University Health Methodist Hospital	Indianapolis	Indiana
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Tampa General Hospital	Tampa	Florida
United States	University of Arizona Sarver Heart Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czechia,  France,  Germany,  Greece,  Italy,  Japan,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)	0, 24, 48, 72, 120 hour or discharge; Day 32
Secondary	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".	Hours 6, 12, 24, 48, and 72
Secondary	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.	From start of infusion up to 6 hours post end of infusion
Secondary	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.	From start of infusion up to 6 hours post end of infusion
Secondary	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.	32 days
Secondary	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.	up to 120 hours (for AEs); up to 32 days (for SAEs)
Secondary	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.	up to 120 hours (for AEs); up to 32 days (for SAEs)
Secondary	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.	up to 120 hours
Secondary	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	through 182 days
Secondary	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	from baseline to Hour 24, 48, and 72
Secondary	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	to 120 hours
Secondary	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	to 120 hours
Secondary	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	to 120 hours
Secondary	Change in Vital Signs From Baseline to 120 Hours - Blood Pressure	The change in baseline for vital signs was reported for each arm.	to 120 hours
Secondary	Change in Vital Signs From Baseline to 120 Hours - Heart Rate	The change in baseline for vital signs was reported for each arm.	to 120 hours
Secondary	Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate	The change in baseline for vital signs was reported for each arm.	to 120 hours
Secondary	Change in Vital Signs From Baseline to 120 Hours - Temperature	The change in baseline for vital signs was reported for each arm.	to 120 hours
Secondary	Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate	The change in baseline for ECGs was reported for each arm.	to 120 hours
Secondary	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.	to 120 hours
Secondary	Change in Physical Measurements From Baseline to 120 Hours	The change in baseline for physical measurements was reported for each arm.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours
Secondary	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.	to 120 hours

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