Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)

NCT00414609 | Completed Phase 3 Results DMC

• 1 other identifier: CSPP100A2340
• Study Type: interventional
• Target: 820
• Locations: 23 countries
• Sites: 23

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).

Conditions

Myocardial Infarction

Keywords

myocardial infarction, aliskiren, heart failure; Post acute myocardial infarction with systolic dysfunction

Outcome Measures

Primary Outcomes (2)

• Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.

  Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.

  Baseline and final visit (after 26 to 36 weeks of treatment)

• Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values

  AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  Extension study (24 weeks)

Secondary Outcomes (10)

• Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes

  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).

• Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)

  Baseline and final visit (after 26 to 36 weeks of treatment)

• Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

  Baseline and final visit (after 26 to 36 weeks of treatment )

• Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography

  Baseline and final visit (after 26 to 36 weeks of treatment)

• Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography

  Baseline and final visit (after 26 to 36 weeks of treatment)

Study Arms (2)

Aliskiren

EXPERIMENTAL

Core Study: Aliskiren ascending doses: 75 mg tablet for 1st week, 150 mg for 2nd week, 300 mg for next 34 weeks orally once daily in the morning. Extension Study: Patients from both the core arms who completed core study and signed informed consent form were included in this arm of extension study. Patients received 150 mg aliskiren tablet orally once a day for two weeks. Patients were then up-titrated to 300 mg aliskiren orally once a day at the discretion of the principal investigator based on their clinical condition for the duration of the study.

Drug: Aliskiren

placebo

PLACEBO COMPARATOR

Core study: placebo for 36 weeks once daily in the morning

Drug: placebo

Interventions

Aliskiren DRUG

Aliskiren was available in 75 mg tablet, 150 mg tablet

Also known as: Tekturna®

Aliskiren

placebo DRUG

Placebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only.

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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
• 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)
• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (23)

Novartis US

Novartis US, New Jersey, United States

Location

Novartis Argentina

Novartis Argentina, Argentina

Location

Novartis Belgium

Novartis Belgium, Belgium

Location

Novartis Canada

Novartis Canada, Canada

Location

Novartis de Colombia S.A.

Bogotá, Colombia

Location

Novartis Czech Republic

Prague, Praha 3, CZ-130 00, Czechia

Location

Novartis Denmark

Novartis Denmark, Denmark

Location

Novartis Germany

Novartis Germany, Germany

Location

Novartis Hungary

Budapest, Budapest, H-1537, Hungary

Location

Novartis Healthcare Private Limited

Worli, Mumbai, 400018, India

Location

Novartis Pharma

Petah Tikva, Petach Tikva, IL-49250, Israel

Location

Novartis Italy

Novartis Italy, Italy

Location

Novartis Netherlands

Novartis Netherlands, Netherlands

Location

Novartis Norway

Novartis Norway, Norway

Location

Novartis Poland Sp. z o.o.

Warsaw, PL-00-710-, Poland

Location

Novartis Russia

Novartis Russia, Russia

Location

Novartis Slovakia

Bratislava, Bratislava Region, SK-821 09, Slovakia

Location

Novartis Korea Ltd.

Seoul, Seoul, 100-803, South Korea

Location

Novartis Spain

Novartis Spain, Spain

Location

Novartis Sweden

Novartis Sweden, Sweden

Location

Novartis Turkey

Istanbul, Istanbul, TR-34353, Turkey (Türkiye)

Location

Novartis UK

Novartis, United Kingdom

Location

Novartis de Venezuela, S.A.

Caracas, 1062, Venezuela

Location

Related Publications (1)

• 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.

  PMID: 21317148 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Heart Failure

Interventions

aliskiren

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis US

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2006
• First Posted: December 21, 2006
• Study Start: December 1, 2006
• Primary Completion: September 1, 2009
• Study Completion: July 1, 2011
• Last Updated: July 13, 2012
• Results First Posted: July 13, 2011

Record last verified: 2012-07

Locations

SE (1); IL (1); NO (1); BE (1); GB (1); SL (1); AR (1); HU (1); NL (1); KR (1); PL (1); CA (1); TU (1); RU (1); CO (1); DK (1); IT (1); US (1); IN (1); VE (1); DE (1); CZ (1); ES (1)