Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF
Condition: Acute Heart Failure
MeSH terms: Heart Failure
Intervention: RLX030; Placebo
Intervention description: 1 mg/mL solution in 6 mL vials; Matching placebo solution to serelaxin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6600.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: acute heart failure,; AHF,; multi-center,; randomized,; double-blind

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:

        Key Inclusion Criteria:

          -  Male or female 18 years of age, with body weight ≤160 kg

          -  Hospitalized for AHF with anticipated requirement of IV therapy for at least 48 hours;
             AHF is defined as including all of the following measured at any time between
             presentation (including the emergency department) and the end of screening:

               -  Persistent dyspnea at rest or with minimal exertion

               -  Pulmonary congestion on chest radiograph

               -  B-type natriuretic peptide (BNP) ≥500 pg/mL or N-terminal (NT)-proBNP ≥2000
                  pg/mL; for patients ≥ 75 years of age or with current atrial fibrillation (at the
                  time of randomization), BNP ≥ 750 pg/mL or NT-proBNP ≥ 3,000 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

          -  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.

        Key Exclusion Criteria:

          -  Dyspnea primarily due to non-cardiac causes

          -  Known history of respiratory disorders requiring the daily use of IV or oral steroids
             (does not include inhaled steroids); need for intubation or the current use of IV or
             oral steroids for chronic obstructive pulmonary disease (COPD)

          -  Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV
             anti-microbial treatment

          -  Clinical evidence of acute coronary syndrome currently or within 30 days prior to
             enrollment.

          -  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

          -  Patients with severe renal impairment defined as pre-randomization estimated
             glomerular filtration rate (eGFR) < 25 mL/min/1.73m2 calculated using the Simplified
             Modification of Diet in Renal Disease (sMDRD) equation, and/or those receiving current
             or planned dialysis or ultrafiltration

          -  Patients with hematocrit <25%, or a history of blood transfusion within the 14 days
             prior to screening, or active life-threatening GI bleeding.

          -  Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased
             ammonia levels, if performed) or history of cirrhosis with evidence of portal
             hypertension such as varices.

          -  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 >40 mmHg on prior or current echocardiogram), and severe mitral
             stenosis

          -  Severe aortic insufficiency or severe mitral regurgitation for which surgical or
             percutaneous intervention is indicated.

          -  Documented, prior to or at the time of randomization, restrictive amyloid
             myocardiopathy, OR acute myocarditis or hypertrophic obstructive, restrictive, or
             constrictive cardiomyopathy (does NOT include restrictive mitral filling patterns seen
             on Doppler echocardiographic assessments of diastolic function).