Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF (RELAX-AHF-ASIA)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Acute Heart Failure

Treatments: Drug: Serelaxin; Drug: Placebo; Other: Standard of CareTherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT02007720

CRLX030A2302

Details and patient eligibility

About

The purpose of the study was to evaluate the efficacy, safety and tolerability of intravenous infusion of serelaxin, when added to standard therapy, in acute heart failure (AHF) patients.

Enrollment: 876 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female ≥ 18 years of age, with body weight ≤160 kg

• Hospitalized for AHF; AHF is defined as including all of the following measured at any time between presentation (including the emergency department and outpatient clinic) and at the end of screening:

  • Persistent dyspnea at rest or with minimal exertion at screening and at the time of randomization
  • Pulmonary congestion on chest radiograph
  • Brain natriuretic peptide (BNP) ≥500 pg/mL or NT-proBNP ≥2,000 pg/mL

• Systolic BP ≥125 mmHg at the start and at the end of screening

• Able to be randomized within 16 hours from presentation to the hospital, including the emergency department and outpatient clinic

• Received intravenous furosemide of at least 40 mg total (or equivalent) at any time between presentation (this includes outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute HF episode

• Renal impairment defined as an estimate glomerular filtration rate using the between presentation and randomization of ≥ 25 and ≤75mL/min/1.73m2, calculated using the Modification of Diet in Renal Disease formula (or modified sMDRD formula according to specific ethnic groups and local practice guidelines).

Exclusion criteria

• Dyspnea primarily due to non-cardiac causes

• Temperature >38.5°C (oral or equivalent), sepsis, active and clinically significant infection requiring IV anti-microbial treatment or known presence or evidence of Human Immunodeficiency Virus (HIV) infection (based on history and/or clinical findings, including laboratory results obtained during screening period).

• Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment

  *Patients with systolic blood pressure >180 mmHg at the end of screening

• AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute

• Hepatic disease unrelated to Heart Failure etiology and as determined by any one of the following: AST and/or ALT values exceeding 3 X ULN and/or bilirubin > 1.5 X ULN at screening or history of hepatic encephalopathy, esophageal varices, or portacaval shunt, or a diagnosis of cirrhosis by any means, or evidence of chronic Hepatitis B (presence of hepatitis B surface antigen production: positive HBsAg), or chronic Hepatitis C infection (presence of Hepatitis C genetic replication: positive Hepatitis C viral RNA, based on history and/or clinical findings, including laboratory results obtained during screening period).

  *Significant uncorrected left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area <1.0 cm2 or mean gradient >50 mmHg on prior or current echocardiogram), and severe mitral stenosis

• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past year with a life expectancy less than 1 year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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876 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Patients will receive continuous intravenous infusion of matching placebo serelaxin for 48 hours.

Treatment:

Drug: Placebo

Other: Standard of CareTherapy

Serelaxin

Experimental group

Description:

Patients will receive continuous intravenous infusion of serelaxin(30 µg/kg/day) for 48 hours.

Treatment:

Drug: Serelaxin

Other: Standard of CareTherapy