Phase 2 N=329 Randomized Quadruple-blind Treatment

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

Heart Failure

Bottom Line

View on ClinicalTrials.gov: NCT03016325 ↗

Enrolled (actual)

329

Serious AEs

24.3%

Results posted

Aug 2020

Primary outcome: Primary: Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion — 8.3; 20.4; 18.3; 21.1 Percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: HNO Donor (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Bristol-Myers Squibb
Primary completion: Jun 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion	8.3; 20.4; 18.3; 21.1; 34.7; 0	—
SECONDARY Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32	-270.88; -364.46; -147.96; -340.74; -416.91; -129.70	—
SECONDARY Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72	-1.5; -1.5; -1.1; -1.7; -1.7; -0.3	—
SECONDARY Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion	2.1; 6.1; 1.4; 2.8; 8.3; 0	—
SECONDARY Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value)	6.3; 20.4; 18.3; 21.1; 29.2; 0	—
SECONDARY Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32	11; 14; 23; 15; 15; 1	—
SECONDARY Number of Participants Who Discontinued Due to Hypotension	4; 8; 7; 13; 16; 0	—
SECONDARY Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure	4; 8; 7; 13; 15; 0	—
SECONDARY Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours	31; 39; 48; 48; 55; 2	—
SECONDARY Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182	3; 3; 11; 12; 9; 0	—
SECONDARY Change in Troponin T From Baseline to Hour 24, 48, and 72	4.11; -1.31; -1.80; -3.45; -8.09; -4.67	—
SECONDARY Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology	5; 2; 5; 4; 3; 0	—
SECONDARY Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry	23; 16; 23; 23; 18; 0	—
SECONDARY Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis	10; 11; 16; 13; 17; 2	—
SECONDARY Change in Vital Signs From Baseline to 120 Hours - Blood Pressure	-6.8; 0.0; -4.3; -7.9; -8.8; -10.3	—
SECONDARY Change in Vital Signs From Baseline to 120 Hours - Heart Rate	-1.8; -9.1; -8.3; -4.6; -6.3; -6.7	—
SECONDARY Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate	-2.6; -3.0; -2.9; -2.6; -1.8; -2.3	—
SECONDARY Change in Vital Signs From Baseline to 120 Hours - Temperature	-0.04; 0.09; 0.04; 0.00; -0.05; -0.47	—
SECONDARY Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate	-5.3; -6.8; -7.1; -5.1; -6.1; 2.0	—
SECONDARY Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration	-17.4; -2.3; -0.1; 10.9; 2.0; -1.5	—
SECONDARY Change in Physical Measurements From Baseline to 120 Hours	0.00; 0.10; -2.87; -2.96; -1.83; -3.58	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L	0.12; -1.38; -0.20; 0.20; -0.09; 5.63	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L	-0.67; -0.70; 1.20; 0.94; 1.38; 1.10	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L	4.01; 0.32; 1.96; 2.15; 1.24; 0.06	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L	148.13; -2.73; -3.22; 30.36; -13.07; -1.00	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL	NA; NA; NA; NA; NA	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L	-0.02; 0.02; 0.04; 0.04; 0.09	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L)	79.38; 74.13; 131.64	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L)	4.33; -1.50; 12.40	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L)	0.18; 0.17; 0.25	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion	4.88; -1.22; -12.34	—
SECONDARY Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion	0.02; -2.62; -5.50	—

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 160mm Hg or heart rate 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03016325). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.