Efficacy, Safety and Tolerability of Sexelaxin When Added to Standard Therapy in AHF
Condition: Acute Heart Failure
MeSH terms: Heart Failure
Intervention: Serelaxin; Placebo; Standard of CareTherapy
Intervention description: Intravenous infusion; Intravenous infusion; This treatment can include but is not limited to intravenous and/or oral diuretics, ACE inhibitors/angiotensin receptor antagonists, β blockers, and aldosterone receptor antagonists, etc.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 876.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Serelaxin,; WHF,; Likert Scale,; RELAX-AHF-ASIA,; RLX030,; AHF,; acute heart failure

Summary:

      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.
    

Eligibility criteria:

        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