Myocardial InfarctionPhase 3NCT00414609
Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)
A Phase 3 study testing Aliskiren in people with Myocardial Infarction, run by Novartis at 23 sites in 23 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Aliskiren
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 820 participants
- Where
- 23 sitesin 23 countries
- Study dates
- Dec 2006to Jul 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
23 sites in 23 countries.
23 sites in 23 countries
About this study
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
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
- Being tested
- Aliskiren, placebo
- Keywords
- myocardial infarction, aliskiren, heart failure, Post acute myocardial infarction with systolic dysfunction
- Medical subject headings
- Myocardial Infarction, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AliskirenDrug
Also called Tekturna®
Aliskiren was available in 75 mg tablet, 150 mg tablet
placeboDrug
Placebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Aliskiren |
| placebo | Placebo comparator | Core study: placebo for 36 weeks once daily in the morning Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Extension study (24 weeks)
Secondary outcomes (10)
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).
Measured: 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)
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.
Measured: Baseline and final visit (after 26 to 36 weeks of treatment)
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.
Measured: 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
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.
Measured: 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
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.
Measured: Baseline and final visit (after 26 to 36 weeks of treatment)
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.
Measured: Baseline(extension study), Month 12 (extension study)
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.
Measured: Baseline (extension study), Month 12 (extension study)
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.
Measured: Baseline(extension study), Month 12 (extension study)
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.
Measured: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24
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)
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionSep 2009
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 820 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis US, Study chair, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00414609
- Sponsor's protocol ID
- CSPP100A2340
- Status last verified
- Jul 2012
- First submitted
- 19 Dec 2006
- Last updated
- 13 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21317148
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00414609
- Acronym / sponsor ID
- CSPP100A2340
- Conditions
- Myocardial Infarction
- Keywords
- myocardial infarction, aliskiren, heart failure, Post acute myocardial infarction with systolic dysfunction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 820 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 21 Dec 2006 (estimated)
- Results
- Posted 13 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aliskiren | Experimental | Drug: AliskirenCore 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. |
| placebo | Placebo comparator | Drug: placeboCore study: placebo for 36 weeks once daily in the morning |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AliskirenAlso: Tekturna®Aliskiren was available in 75 mg tablet, 150 mg tablet | Drug | Aliskiren |
| placeboPlacebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only. | Drug | placebo |
Primary outcome
Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)
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.
Extension Study: Percentage of Participants With Deaths, Serious Adverse Events (SAEs), Discontinuation for Adverse Events (AEs) and Discontinuations for Abnormal Lab Values
Time frame: Extension study (24 weeks)
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.
10 secondary outcomes
Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes
Time frame: 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)
Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)
Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: 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
Time frame: 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
Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)
Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12
Time frame: Baseline(extension study), Month 12 (extension study)
Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12
Time frame: Baseline (extension study), Month 12 (extension study)
Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12
Time frame: Baseline(extension study), Month 12 (extension study)
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change
Time frame: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter
Time frame: 24 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21317148Solomon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis US study chair
Novartis
23 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aliskiren in people with Myocardial Infarction, run by Novartis at 23 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Argentina, Belgium, Canada, Colombia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study. (time frame: Baseline and final visit (after 26 to 36 weeks of treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00414609, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2012.