Six Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality in Patients With Acute Decompensated Heart Failure (ASTRONAUT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00894387
First received: May 5, 2009
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

This study evaluated the effect of early initiation of aliskiren therapy, compared to standard therapy, in the reduction of cardiovascular death and heart failure re-hospitalization events within 6 months, in congestive heart failure (CHF) patients hospitalized for an episode of acute decompensated heart failure.


Condition Intervention Phase
Acute Decompensated Heart Failure
Congestive Heart Failure
Drug: Aliskiren
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the 6 Months Efficacy and Safety of Aliskiren Therapy on Top of Standard Therapy, on Morbidity and Mortality When Initiated Early After Hospitalization for Acute Decompensated Heart Failure

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to Event Analysis: Number of Patients Experienced the First Confirmed Occurrence of Either Cardiovascular Death or Heart Failure (HF) Re-hospitalization Within 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time to first confirmed occurrence of either cardiovascular death or heart failure re-hospitalization within 6 months of randomization was the primary efficacy variable. For the primary efficacy analysis, an event will be considered for the analysis if it occurs on or before Day 190 (189 days from randomization). The primary composite endpoint is the the composite of cardiovascular death or heart faliure re-hospitalization within 6 months.


Secondary Outcome Measures:
  • Time to Event Analysis: Number of Patients Experienced the First Confirmed Occurrence of Either Cardiovascular Death or Heart Failure (HF) Re-hospitalization Within 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Time to first confirmed occurrence of either cardiovascular death or heart failure re-hospitalization within 12 months of randomization was the key secondary efficacy variable. For the primary efficacy analysis, an event will be considered for the analysis if it occurs on or before Day 395 (394 days from randomization). The secondary composite endpoint is the the composite of cardiovascular death or heart faliure re-hospitalization within 12 months.

  • Change From Baseline in the Clinical Summary Score to 1 Month, 6 Months and 12 Months [ Time Frame: Baseline, 1 months, 6 months and 12 months ] [ Designated as safety issue: No ]
    Symptom reduction and reduction in physical limitations was assessed using the clinical summary score of the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ is a self-administered questionnaire and contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Health-Related Quality of Life (QoL), including limitations, frequency, bother, change in condition, understanding, levels of enjoyment and satisfaction. Each scale score was calculated as the mean of its item scores and transformed to a 0-100 scale, with higher score indicating higher level of functioning. A score of 100 represents perfect health whereas a score of 0 represents death. A positive change in score from baseline indicates an improvement.

  • Time to Event Analysis: Number of Patients With First Cardiovascular (CV) Event Hospitalized for an Acute Heart Faliure (AHF) Event Within 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A cardiovascular event defined as CV death, heart faliure re-hospitalization, non-fatal myocardial infarction (MI), nonfatal stroke, sudden death with resuscitation.

  • Time to Event Analysis: Number of Patients With All-cause Mortality Hospitalized for an AHF Event Within 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level at 1 Month, 6 Months, and 12 Months [ Time Frame: Baseline, 1 month, 6 months and 12 months ] [ Designated as safety issue: No ]
    The reported Least square means, and Confidential Interval were from a repeated measures model on log transformed NT-proBNP data containing treatment, visit, and region as factors, log baseline NT-proBNP as a continuous covariate and treatment by visit and visit by log baseline NT-proBNP as interaction terms.

  • Time to Event Analysis: Number of Patients With First Cardiovascular (CV) Event Hospitalized for an Acute Heart Faliure (AHF) Event Within 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A cardiovascular event defined as CV death, heart faliure re-hospitalization, non-fatal myocardial infarction (MI), nonfatal stroke, sudden death with resuscitation.


Enrollment: 1639
Study Start Date: May 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aliskiren
Randomized patients in this arm received, Aliskiren 150 mg once daily for 2 weeks. From week 2 upto 6 months , patients who could tolerate study medication were up-titrated to aliskiren 300 mg once daliy.
Drug: Aliskiren
Aliskiren 150 mg and Aliskiren 300 mg
Other Names:
  • Aliskiren®,
  • Tekturna®,
  • Rasilez®,
  • SPP100
Placebo Comparator: Placebo
Randomized patients in this arm received matching placebo of Aliskiren. At week 2, Patients who could tolerate study medication were up-titrated to matching placebo of 300 mg aliskiren.
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patient hospitalized with a primary diagnosis of worsening heart failure ≥ 18 years of age, male or female.
  • Patients with a diagnosis of acute heart failure expressed by symptoms (dyspnea or fatigability - NYHA Class III-IV) and signs of fluid overload (i.e., jugular venous distension, edema or positive rales auscultation or pulmonary congestion on chest x-ray) at the time of hospitalization.

    • LVEF < 40% (measured within the last 6 months).
    • Hospitalization for ADHF and remain "stabilized" for at least 6 hours (defined as SBP ≥ 110 mm Hg after acute decompensated episode) and did not receive IV vasodilators (other than nitrates) and/or IV inotropic drugs at anytime from ADHF presentation to time of randomization.
  • Elevated BNP at Visit 1 or at randomization (BNP ≥ 400 pg/ml).
  • Patients with a history of chronic heart failure on standard therapy defined as requiring HF treatment for at least 30 days before the current hospitalization (NYHA Class II - IV).

Exclusion Criteria:

  • Patients that required any use of IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for worsening HF to randomization.
  • Concomitant use of ACEI and ARB at randomization.
  • Right heart failure due to pulmonary disease.
  • Diagnosis of postpartum cardiomyopathy.
  • Myocardial infarction or cardiac surgery, including percutaneous transluminal coronary angioplasty (PTCA), within past 3 months.
  • Patients with a history of heart transplant or who are on a transplant list.
  • Unstable angina or coronary artery disease likely to require coronary artery bypass graft (CABG) or PTCA before randomization.

Other protocol-defined inclusion/exclusion criteria applied.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00894387

  Show 308 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00894387     History of Changes
Other Study ID Numbers: CSPP100A2368, 2009-010236-18
Study First Received: May 5, 2009
Results First Received: August 2, 2013
Last Updated: October 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
elevated BNP
reduced LVEF
Acute Heart Failure
Cardiovascular death
CHF
hospitalization
morbi-mortality trial
outcome study
endpoint driven
plasma renin activity
renin angiotensin
aldosterone system
direct renin inhibitors
BNP
KCCQ
eGFR

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014