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

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ClinicalTrials.gov Identifier: NCT01870778
Recruitment Status : Completed
First Posted : June 6, 2013
Results First Posted : March 30, 2018
Last Update Posted : March 30, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Acute Heart Failure Drug: RLX030 Drug: Placebo Phase 3

Detailed Description:
This Phase IIIb outcome study in AHF patients was 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 were followed for a period of 180 days, and were 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : October 2, 2013
Actual Primary Completion Date : January 23, 2017
Actual Study Completion Date : February 1, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arms and Interventions
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Arm Intervention/treatment
Experimental: Serelaxin (RLX030)
Participants received continuous intravenous infusion of serelaxin 30 ug/kg/day for 48 hours.
 Drug: RLX030
1 mg/mL solution in 6 mL vials
Placebo Comparator: Placebo
Participants received continuous intravenous infusion of matching placebo to serelaxin for 48 hours.
 Drug: Placebo
Matching placebo solution to serelaxin


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Confirmed Cardiovascular (CV) Death Through Day 180 [ Time Frame: 180 days ]
    The percentage of participants with an adjudicated CV death through day 180 was assessed.

  2. Percentage of Participants With Worsening of Heart Failure (WHF) Through Day 5 [ Time Frame: Day 5 ]
    The percentage of participants with WHF through day 5 was assessed.


Secondary Outcome Measures :
  1. Percentage of Participants With All-cause Death Through Day 180 [ Time Frame: 180 days ]
    The percentage of participants with all-cause death through day 180 was assessed.

  2. Length of Total Hospital Stay (LOS) During the Index Acute Heart Failure (AHF) Hospitalization [ Time Frame: 180 days (Participants still in the hospital at Day 60 were censored at Day 60) ]
    Length of stay was defined as the index hospitalization discharge date and time minus the baseline date and time plus 1 day.

  3. Percentage of Participants With First Occurrence of Adjudicated CV Death or Adjudicated Re-hospitalization [ Time Frame: 180 days ]
    The percentage of participants with adjudicated CV death or adjudicated re-hospitalization through day 180 was assessed.

  4. Length of Intensive Care Unit (ICU) and/or Coronary Care Unit (CCU) Stay for the Index AHF Hospitalization [ Time Frame: 180 days (Patients still in the hospital at Day 60 were censored at Day 60) ]
    Length of stay was defined as the hospitalization discharge date and the time minus the baseline date and time plus 1 day.

  5. Percentage of Participants With First Improvement Since Baseline in Congestive Signs and Symptoms of Heart Failure [ Time Frame: From baseline to Day 5 ]
    The percentage of participants with first improvement since baseline in congestive signs and symptoms was assessed. The signs and symptoms included exertional dyspnea, orthopnea, rales, jugular venous pressure and peripheral edema/pre-sacral edema.

  6. Change From Baseline in hsTroponin T Biomarker [ Time Frame: Baseline, Day 2, Day 5 and Day 14 ]
    Blood samples were collected to assess the change from baseline in hsTroponin T. The geometric least square mean (LSM) of the ratio of the post-baseline value to the baseline value is presented.

  7. Change From Baseline in NT-proBNP Biomarker [ Time Frame: Baseline, Day 2, Day 5 and Day 14 ]
    Blood samples were collected to assess the change from baseline in NT-proBNP. The ratio of the post-baseline value to the baseline value is presented.

  8. Change From Baseline in Cystatin C Biomarker [ Time Frame: Baseline, Day 2, Day 5 and Day 14 ]
    Blood samples were collected to assess the change from baseline in Cystatin C. The ratio of the post-baseline value to the baseline value is presented.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01870778


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] March 3, 2017
Study Protocol  [PDF] February 18, 2015

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01870778    
Other Study ID Numbers: CRLX030A2301
2013-001498-25 ( EudraCT Number )
First Posted: June 6, 2013    Key Record Dates
Results First Posted: March 30, 2018
Last Update Posted: March 30, 2018
Last Verified: March 2018
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
acute heart failure,
AHF,
multi-center,
randomized,
double-blind
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases