Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF (RELAX-AHF-2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01870778
First received: June 3, 2013
Last updated: May 18, 2016
Last verified: May 2016
  Purpose
The purpose of the study to evaluate the efficacy, safety and tolerability of intravenous infusion of serelaxin, when added to standard therapy, in acute heart failure (AHF) patients.

Condition Intervention Phase
Acute Heart Failure
Drug: RLX030
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to confirmed cardiovascular (CV) death during the follow-up period of 180 days [ Time Frame: From baseline to 180 days ] [ Designated as safety issue: No ]
    Time-to-event is computed as the number of days from randomization to CV death.

  • Time to worsening of heart failure (WHF) through Day 5 (considering death in the 5-day) [ Time Frame: From Baseline to Day 5 ] [ Designated as safety issue: No ]
    Time to event is computed as the number of days from randomization to WHF


Secondary Outcome Measures:
  • Time to all-cause death through Day 180 [ Time Frame: From baseline to 180 days ] [ Designated as safety issue: No ]
    Time to event is computed as the number of days from randomization to all cause death

  • Length of total hospital stay (LOS) during the index acute heart failure (AHF) hospitalization [ Time Frame: From baseline to 180 days ] [ Designated as safety issue: No ]
    Length of stay will be defined as the index hospitalization discharge date and time minus the baseline date and time plus 1 day

  • Time to first occurrence of the composite endpoint of CV death or rehospitalization due to heart failure or renal failure through day 180 [ Time Frame: From baseline to 180 days ] [ Designated as safety issue: No ]
    Time to first is computed as the number of days from randomization to event of interest

  • Length of Intensive Care Unit (ICU) and/or Coronary care unit (CCU) stay for the index AHF hospitalization [ Time Frame: From baselint to 180 days ] [ Designated as safety issue: No ]
    Length of stay will be defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day

  • Change from baseline in congestive signs and symptoms of heart failure through Day 5 [ Time Frame: From baseline to Day 5 ] [ Designated as safety issue: No ]
    Change from baseline in congestive signs and symptoms of HF through Day 5 will be analyzed by displaying the change in percentage of patients by treatment and time points for each of the signs and symptoms variables.

  • Change from baseline in selected biomarkers from baseline through Day 14 in a subset [ Time Frame: From baseline to Day 14 ] [ Designated as safety issue: No ]
  • Number of patients reported with total adverse events, serious adverse events and death [ Time Frame: For the safety evaluation, all adverse events will be collected from signing of the informed consent form through Day 5 for non-serious AEs and through Day 14 for serious AEs. ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of intravenous serelaxin in AHF patients, number of patients with total adverse events, serious adverse events and death will be analyzed.


Estimated Enrollment: 6800
Study Start Date: October 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
patients will receive continuous intravenous infusion of matching placebo serelaxin for 48 hours.
Drug: Placebo
placebo
Experimental: Serelaxin
Patients will receive continuous intravenous infusion of serelaxin for 48 hours.
Drug: RLX030
intravenous infusion

Detailed Description:
This Phase IIIb outcome study in AHF patients is designed as a multicenter, randomized, double-blind, placebo-controlled, event-driven study in order to assess the efficacy, safety and tolerability of intravenous infusion of serelaxin or placebo. The AHF patients randomized to either serelaxin or placebo in the study will be followed for a period of 180 days, and are required to receive standard-of-care background HF management during both the index hospitalization and post discharge according to regional or local guidelines/institutional standards.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female 18 years of age, with body weight ≤160 kg
  • Hospitalized for AHF with anticipated requirment 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
    • BNP ≥500 pg/mL or 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 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 eGFR < 25 mL/min/1.73m2 calculated using the 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01870778

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 658 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01870778     History of Changes
Other Study ID Numbers: CRLX030A2301  2013-001498-25 
Study First Received: June 3, 2013
Last Updated: May 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
acute heart failure,
AHF,
multi-center,
randomized,
double-blind

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2016