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

Study Overview
=================
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).

Official Title
-----------------
A Multicenter, Prospective, Randomized, Open-label Study to Assess the Effect of Serelaxin Versus Standard of Care in Acute Heart Failure (AHF) Patients

Conditions
-----------------
Acute Heart Failure (AHF)

Intervention / Treatment
-----------------
* Drug: Serelaxin
* Drug: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Serelaxin + Standard of Care<br>Serelaxin (30 µg/kg/day) as continuous 48 hour intravenous infusion plus standard of care. | Drug: Serelaxin<br>* 30 µg/kg/day IV infusion<br>* Other names: RLX030;Drug: Standard of Care<br>* 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.<br>|
| Other: Standard of Care (SOC)<br>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. | Drug: Standard of Care<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Worsening Heart Failure (WHF) / All Cause of Deaths Through Day 5 | 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. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With In-hospital Worsening Heart Failure/All-Cause Death/Readmission for Heart Failure Through Day 14 | 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. | 14 days | 
| Percentage of Participants With Persistent Sign or Symptoms of Heart Failure / Non-Improvement at Any Post Baseline Visit Through Day 5 | Persistent or non-improvement in any signs or symptoms of HF at any post baseline visit up to Day 5. | 5 days | 
| Percentage of Participants With Renal Deterioration at Any Post Baseline Visit Through Day 14 | Renal deterioration is defined as > or = 0.3 mg/dL increase from screening in serum creatinine. | 14 days | 
| Length of Index Hospital Stay | Length of stay (in hours) is defined as the index hospitalization discharge date and time minus the index hospitalization start date and time. | 30 Days | 
| 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. | 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). | Baseline, Day 5, Day 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AHF,, RLX030,, SOC,, WHF,, RELAX-AHF-EU, Renal Impairment