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

Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414609
• Other study ID #: CSPP100A2340
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2006
• Last updated: July 5, 2012
• Start date: December 2006
• Est. completion date: July 2011

Study information

• Verified date: July 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: Ministry of Social Affairs, Public Health and the EnvironmentBrazil: National Health Surveillance AgencyCanada: Canadian Institutes of Health ResearchColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIndia: Ministry of HealthIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: The Italian Medicines AgencySouth Korea: Korea Food and Drug Administration (KFDA)Netherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencyPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Pharmacological Committee, Ministry of HealthSlovakia: State Institute for Drug ControlSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyVenezuela: Ministry of Health and Social Development
• Study type: Interventional

Clinical Trial 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).

Other known NCT identifiers

• NCT00699075

Recruitment information / eligibility

• Status: Completed
• Enrollment: 820
• Est. completion date: July 2011
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• Aliskiren
Aliskiren was available in 75 mg tablet, 150 mg tablet
• placebo
Placebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only.

Locations

Country	Name	City	State
Argentina	Novartis Argentina	Novartis Argentina
Belgium	Novartis Belgium	Novartis Belgium
Canada	Novartis Canada	Novartis Canada
Colombia	Novartis de Colombia S.A.	Bogota
Czech Republic	Novartis Czech Republic	Praha	Praha 3
Denmark	Novartis Denmark	Novartis Denmark
Germany	Novartis Germany	Novartis Germany
Hungary	Novartis Hungary	Budapest
India	Novartis Healthcare Private Limited	Worli, Mumbai
Israel	Novartis Pharma	Petach Tikva
Italy	Novartis Italy	Novartis Italy
Korea, Republic of	Novartis Korea Ltd.	Seoul
Netherlands	Novartis Netherlands	Novartis Netherlands
Norway	Novartis Norway	Novartis Norway
Poland	Novartis Poland Sp. z o.o.	Warszawa
Russian Federation	Novartis Russia	Novartis Russia
Slovakia	Novartis Slovakia	Bratislava
Spain	Novartis Spain	Novartis Spain
Sweden	Novartis Sweden	Novartis Sweden
Turkey	Novartis Turkey	Istanbul
United Kingdom	Novartis UK	Novartis
United States	Novartis US	Novartis US	New Jersey
Venezuela	Novartis de Venezuela, S.A.	Caracas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Venezuela,  Argentina,  Belgium,  Canada,  Colombia,  Czech Republic,  Denmark,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Russian Federation,  Slovakia,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes	Composite outcome 1 included: Cardiovascular (CV) Death, hospitalization for heart failure (HF), or absolute reduction in Left Ventricular Ejection Fraction (LVEF) greater than 6%. Composite outcome 2 included: CV Death, hospitalization for HF, recurrent Myocardial Infarction, Stroke, or Resuscitated Sudden Death. LVEF was measured at baseline and final visit. All other events were adjudicated by a blinded external committee. Each composite endpoint analysis was based on (a) the percent of patients with that endpoint and (b) days in study to 1st event (or last exposure if no event occurred).	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).	No
Secondary	Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)	Change from baseline to end of study in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal. Baseline LVEDV was a covariate.	Baseline and final visit (after 26 to 36 weeks of treatment)	No
Secondary	Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)	Change from baseline to end of study in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal. Baseline LVEF was a covariate.	Baseline and final visit (after 26 to 36 weeks of treatment )	No
Secondary	Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography	Change from baseline to end of study in infarction segment length (ISL) (%) as measured by echocardiography. This is the length of the myocardial infarction segment as a percentage of the total cavity perimeter length as calculated by the echocardiography lab. Baseline ISL was a covariate.	Baseline and final visit (after 26 to 36 weeks of treatment)	No
Secondary	Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography	Change from baseline to end of study in Wall Motion Score (WMS) as measured by echocardiography. WMS was obtained by examining multiple segments of the left ventricle and assigning each segment a score based on myocardial thickening: 1 for normal, 2 for hypokinetic; 3 for akinetic; and 4 for dyskinetic. The WMS was obtained as the average score for the segments visualized and was calculated by the echocardiography lab. Possible values range from 1 to 5. Higher scores are considered worse. Baseline WMS was a covariate.	Baseline and final visit (after 26 to 36 weeks of treatment)	No
Secondary	Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12	Change from baseline to Month 12 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(extension study), Month 12 (extension study)	No
Secondary	Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12	Change from baseline to Month 12 in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. LVEDV is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal.	Baseline (extension study), Month 12 (extension study)	No
Secondary	Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12	Change from baseline to Month 12 in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages > 55% are considered normal.	Baseline(extension study), Month 12 (extension study)	No
Secondary	Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change	Orthostatic blood pressure change is defined as a decrease of at least 20 mmHg in systolic blood pressure or a decrease of at least 10 mmHg in diastolic blood pressure when a patient moves from a sitting position to a standing position. A patient could show orthostatic blood pressure change at more than one visit. End of study is Month 24 or early discontinuation.	Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24	No
Secondary	Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter	Fasting blood samples were collected throughout the study and were analyzed at a central laboratory. Percentage of participants with the following clinically significant laboratory values are reported: Potassium <3.5 mmol/L; Low value (Normal reference range: 3.5- 5.3); Potassium >5.5 mmol/L and Potassium >6.0 mmol/L; High values (Normal reference range: 3.5-5.3); Creatinine >176.8 µmol/L; High value (Normal reference range= Male: 62- 106 and Female 44- 80); Blood Urea Nitrogen (BUN) >14.28; High value (Normal reference range: 2.1- 8.9)	24 Months	No