A multicenter, randomized, double-blind, placebo- controlled phase III study to evaluate the efficacy, safety and tolerability of Serelaxin when added to standard therapy in acute heart failure patients

Phase 3

Completed

Conditions: Acute Heartfailure
10019280

Registration Number: NL-OMON45125

Lead Sponsor: ovartis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 125

Inclusion Criteria

- Male or female *18 years of age, with body weight *160 kg
- Hospitalized for AHF with the anticipated requirement of intravenous therapy (including IV diuretics) for at least 48 hours, i.e. persistent dyspnea at rest or with minimal exertion at screening and at the time of randomization, despite standard background therapy for acute heart failure including the protocol required intravenous furosemide of at least 40 mg total (or equivalent), pulmonary congestion on chest radiograph, BNP * 500 pg/mL or NT-proBNP * 2,000 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. Time from presentation to start of furosemide administration should be less than 6 hours.
- Impaired renal function defined as an eGFR between presentation and randomization
of * 25 and *75mL/min/1.73m2, calculated using the sMDRD equation.

Exclusion Criteria

- Dyspnea due to non-cardiac causes due to non-cardiac causes such as acute or chronic respiratory disorders or infections (i.e., severe chronic obstructive pulmonary disease, bronchitis, pneumonia), which may interfere with the ability to interpret the primary cause of dyspnea.
-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 COPD.
- Patients with blood pressure > 180 mmHg at the time of randomization or persistent heart rate >130 bpm.
- Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV antimicrobial
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 eGFR < 25
mL/min/1.73m2 calculated using the sMDRD equation, and/or those receiving current or
planned dialysis or ultrafiltration.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy assessment:<br /><br>Time to confirmed CV death during a follow-up period of 180 days.<br /><br>Time to first occurrence of worsening of heart failure through Day5<br /><br>(considering death in the 5-day period as WHF event)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Key secondary assessments:<br /><br>* Time to all-cause death during a follow-up period of 180 days<br /><br>* Length of total hospital stay for the index AHF hospitalization<br /><br>* Time to first occurrence of the composite endpoint of CV death or<br /><br>rehospitalization due to heart failure/renal failure, during a follow-up period<br /><br>of 180 days.<br /><br><br /><br>Other secondary efficacy assessments:<br /><br>* Length of ICU and/or CCU stay for the index AHF hospitalization<br /><br>* Change from baseline in congestive signs and symptoms of HF through Day 5<br /><br>* Change from baseline in selected biomarkers from baseline through Day 14 in a<br /><br>subset of randomized patients</p><br>