Clinical trial NCT00414609: Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)
Official title: A 36-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Including a 2 Year Extension Study to Evaluate Efficacy and Safety of Aliskiren on the Prevention of Left Ventricular Remodeling in High Risk Post-acute Myocardial Infarction Patients When Added to Optimized Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Infarction
Keywords: myocardial infarction, aliskiren, heart failure
Post acute myocardial infarction with systolic dysfunction
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-21
Enrollment: 820
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The core and extension studies assessed the safety and efficacy of aliskiren when added to optimized standard therapy in patients that have had a high risk acute myocardial infarction (heart attack).


Eligibility criteria: Core Study Inclusion Criteria:

* Male or female patients 18 years and older.
* Patients within 7-42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction.
* Documented left ventricular systolic dysfunction associated with the qualifying acute myocardial.
* Patients must be on stable doses of the following concomitant medications for at least 2 weeks prior to Visit 1 unless contraindicated due to intolerance:

  * A Beta-blocker
  * An Anti-platelet agent
  * A Statin
  * An evidence-based dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) but not both.
* Qualifying Echocardiogram at Visit 1:

Core Study Exclusion Criteria:

* Patients requiring both Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) combination therapy at V1 or any time during the study.
* Severe refractory hypertension defined as mean sitting systolic blood pressure (MSSBP) ≥ 180 mmHg and/or mean sitting diastolic blood pressure (MSDBP) ≥ 110 mmHg) at Visit 2.
* Cardiogenic shock or systolic BP \< 100 mmHg or diastolic \< 60 mmHg within the 24 hours prior to Visits 1 or 2
* Estimated Glomerular Filtration Rate (eGFR) \< 30 ml/min/1.73m2 using the MDRD formula at Visit 1.
* Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1

Extension Study Inclusion Criteria:

* Male or female patients who completed the core study through Visit 10 while on double-blind study drug
* Patients who were able to participate in the study, and who consented to do so after the purpose and nature of the study had been clearly explained to them (written informed consent)

Extension Study Exclusion Criteria:

* New York Heart Association (NYHA) class IV Congestive Heart Failure at Visit 1 (Core study Visit 10)
* Symptomatic hypotension or reported systolic blood pressure (BP) \< 90 mmHg within 24 hours prior to Visit 1 (Core study Visit 10)
* Known Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73m\^2 using the Modification of Diet in Renal Disease (MDRD) formula at Visit 1 (Core study Visit 10)
* Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL)
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant Unless post-menopausal or using an acceptable method of contraception
* Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or was likely to prevent the patient from complying with the requirements or completing the study

Other protocol-defined inclusion/exclusion criteria applied

Primary outcomes:
measure: Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
timeFrame: Baseline and final visit (after 26 to 36 weeks of treatment)
measure: Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values
timeFrame: Extension study (24 weeks)
Secondary outcomes:
measure: Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes
timeFrame: LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).
measure: Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)
timeFrame: Baseline and final visit (after 26 to 36 weeks of treatment)
measure: Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline and final visit (after 26 to 36 weeks of treatment )
measure: Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography
timeFrame: Baseline and final visit (after 26 to 36 weeks of treatment)
measure: Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography
timeFrame: Baseline and final visit (after 26 to 36 weeks of treatment)
measure: Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12
timeFrame: Baseline(extension study), Month 12 (extension study)
measure: Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12
timeFrame: Baseline (extension study), Month 12 (extension study)
measure: Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12
timeFrame: Baseline(extension study), Month 12 (extension study)
measure: Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change
timeFrame: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24
measure: Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter
timeFrame: 24 Months
Other outcomes:
Locations:
city: Novartis US
country: United States
facility: Novartis US
state: New Jersey
city: Novartis Argentina
country: Argentina
facility: Novartis Argentina
city: Novartis Belgium
country: Belgium
facility: Novartis Belgium
city: Novartis Canada
country: Canada
facility: Novartis Canada
city: Bogota
country: Colombia
facility: Novartis de Colombia S.A.
city: Praha
country: Czech Republic
facility: Novartis Czech Republic
state: Praha 3
city: Novartis Denmark
country: Denmark
facility: Novartis Denmark
city: Novartis Germany
country: Germany
facility: Novartis Germany
city: Budapest
country: Hungary
facility: Novartis Hungary
city: Worli, Mumbai
country: India
facility: Novartis Healthcare Private Limited
city: Petach Tikva
country: Israel
facility: Novartis Pharma
city: Novartis Italy
country: Italy
facility: Novartis Italy
city: Seoul
country: Korea, Republic of
facility: Novartis Korea Ltd.
city: Novartis Netherlands
country: Netherlands
facility: Novartis Netherlands
city: Novartis Norway
country: Norway
facility: Novartis Norway
city: Warszawa
country: Poland
facility: Novartis Poland Sp. z o.o.
city: Novartis Russia
country: Russian Federation
facility: Novartis Russia
city: Bratislava
country: Slovakia
facility: Novartis Slovakia
city: Novartis Spain
country: Spain
facility: Novartis Spain
city: Novartis Sweden
country: Sweden
facility: Novartis Sweden
city: Istanbul
country: Turkey
facility: Novartis Turkey
city: Novartis
country: United Kingdom
facility: Novartis UK
city: Caracas
country: Venezuela
facility: Novartis de Venezuela, S.A.
Study officials:
affiliation: Novartis
name: Novartis US
role: STUDY_CHAIR
References:
citation: Solomon SD, Shin SH, Shah A, Skali H, Desai A, Kober L, Maggioni AP, Rouleau JL, Kelly RY, Hester A, McMurray JJ, Pfeffer MA; Aliskiren Study in Post-MI Patients to Reduce Remodeling (ASPIRE) Investigators. Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction. Eur Heart J. 2011 May;32(10):1227-34. doi: 10.1093/eurheartj/ehq522. Epub 2011 Feb 10.