Effect of Serelaxin Versus Standard of Care in Acute Heart Failure (AHF) Patients

Phase 3

Terminated

Conditions: Acute Heart Failure (AHF)

Interventions: Drug: Serelaxin
Drug: Standard of Care

Registration Number: NCT02064868

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This was a multinational, multicenter, randomized, open-label study to confirm and expand the efficacy, safety and tolerability evidence of 48 hours intravenous infusion of serelaxin (30 micrograms/kg/day) when added to Standard of Care (SoC) in patients admitted to hospital for Acute Heart Failure (AHF).

Detailed Description: This study was aimed at generating clinical evidence, especially on the short term period (in-hospital and at 30 days) to complement existing and future serelaxin data sets in Acute Heart Failure (AHF).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2666

Inclusion Criteria

Systolic blood pressure ≥ 125 mmHg
Admitted for Acute Heart Failure (AHF)
Received intravenous furosemide (or equivalent) at any time between presentation and the start of screening
eGFR on admission: ≥ 25 and ≤75 mL/min/1.73 m^2

Exclusion Criteria

Dyspnea (non-cardiac causes)
T > 38.5°C
Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
Significant left ventricular outflow obstruction, uncorrected, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area <1.0 cm^2 or mean gradient >50 mmHg on prior or current echocardiogram), severe aortic regurgitation and severe mitral stenosis.
AHF due to significant arrhythmias
Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Serelaxin + Standard of Care	Serelaxin	Serelaxin (30 µg/kg/day) as continuous 48 hour intravenous infusion plus standard of care.
Serelaxin + Standard of Care	Standard of Care	Serelaxin (30 µg/kg/day) as continuous 48 hour intravenous infusion plus standard of care.
Standard of Care (SOC)	Standard of Care	All patients were required to receive standard of care background heart failure (HF) management during the study, according to local guidelines/international standards. This treatment can include but is not limited to intravenous and/or oral diuretics, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor antagonists, beta blockers and aldosterone receptor antagonists, etc.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Worsening Heart Failure (WHF) / All Cause of Deaths Through Day 5	5 days	In-hospital WHF through Day 5 post-randomization included worsening signs and/or symptoms of heart failure that required an intensification of intravenous therapy for heart failure or mechanical ventilation, renal or circulatory support. A central event adjudication committee was appointed to oversee the WHF primary endpoint adjudication.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Persistent Sign or Symptoms of Heart Failure / Non-Improvement at Any Post Baseline Visit Through Day 5	5 days	Persistent or non-improvement in any signs or symptoms of HF at any post baseline visit up to Day 5.
Length of Index Hospital Stay	30 Days	Length of stay (in hours) is defined as the index hospitalization discharge date and time minus the index hospitalization start date and time.
Percentage of Participants With In-hospital Worsening Heart Failure/All-Cause Death/Readmission for Heart Failure Through Day 14	14 days	WHF/death/readmission for heart failure through Day 14. WHF/deaths through Day 5 were adjudicated and confirmed by the Clinical Endpoint Committee, WHF/deaths after Day 5 through Day 14 and readmission through Day 14 were as reported by the investigators.
Percentage of Participants With Renal Deterioration at Any Post Baseline Visit Through Day 14	14 days	Renal deterioration is defined as \> or = 0.3 mg/dL increase from screening in serum creatinine.
Percentage of Participants With Adverse Events as Assessment of Safety and Tolerability of Serelaxin in AHF Patients	Adverse Events (AE): 5 Days / Serious Adverse Events (SAE): 14 days / All cause deaths 30 days
Change From Baseline in Health-related Quality of Life Index Value, Assessed by EuroQoL EQ-5D-5L Questionnaire.	Baseline, Day 5, Day 14	EQ-5D-5L is a questionnaire designed to assess health status in adults consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The results were converted into a single index value using UK as the reference country for all countries. Range -0.3 (worst possible state) to 1 (best possible state).