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

5 juillet 2012 mis à jour par: Novartis

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).

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

820

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Novartis Germany, Allemagne
        • Novartis Germany
  • Argentine
      • Novartis Argentina, Argentine
        • Novartis Argentina
  • Belgique
      • Novartis Belgium, Belgique
        • Novartis Belgium
  • Canada
      • Novartis Canada, Canada
        • Novartis CANADA
  • Colombie
      • Bogota, Colombie
        • Novartis de Colombia S.A.
  • Corée, République de
      • Seoul, Corée, République de, 100-803
        • Novartis Korea Ltd.
  • Danemark
      • Novartis Denmark, Danemark
        • Novartis Denmark
  • Espagne
      • Novartis Spain, Espagne
        • Novartis Spain
  • Fédération Russe
      • Novartis Russia, Fédération Russe
        • Novartis Russia
  • Hongrie
      • Budapest, Hongrie, H-1537
        • Novartis Hungary
  • Inde
      • Worli, Mumbai, Inde, 400018
        • Novartis Healthcare Private Limited
  • Israël
      • Petach Tikva, Israël, IL-49250
        • Novartis Pharma
  • Italie
      • Novartis Italy, Italie
        • Novartis Italy
  • Norvège
      • Novartis Norway, Norvège
        • Novartis Norway
  • Pays-Bas
      • Novartis Netherlands, Pays-Bas
        • Novartis Netherlands
  • Pologne
      • Warszawa, Pologne, PL-00-710-
        • Novartis Poland Sp. z o.o.
  • Royaume-Uni
      • Novartis, Royaume-Uni
        • Novartis UK
  • République tchèque
    • Praha 3
      • Praha, Praha 3, République tchèque, CZ-130 00
        • Novartis Czech Republic
  • Slovaquie
      • Bratislava, Slovaquie, SK-821 09
        • Novartis Slovakia
  • Suède
      • Novartis Sweden, Suède
        • Novartis Sweden
  • Turquie
      • Istanbul, Turquie, TR-34353
        • Novartis Turkey
  • Venezuela
      • Caracas, Venezuela, 1062
        • Novartis de Venezuela, S.A.
  • États-Unis
    • New Jersey
      • Novartis US, New Jersey, États-Unis
        • Novartis US

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Aliskiren

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.
Médicament: Aliskiren
Aliskiren was available in 75 mg tablet, 150 mg tablet
Autres noms:
  • Tekturna®
Comparateur placebo: placebo
Core study: placebo for 36 weeks once daily in the morning
Médicament: placebo
Placebo tablets matching aliskiren for 36 weeks once daily in the morning for core period only.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Core Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) as Measured by Echocardiography at End of Study.
Délai: 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.
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
Délai: 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.
Extension study (24 weeks)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Core Study: Time to First Occurrence for the Composite Endpoints of Echocardiogram and Adjudicated Outcomes
Délai: 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).
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).
Core Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV)
Délai: Baseline and final visit (after 26 to 36 weeks of treatment)
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)
Core Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Délai: Baseline and final visit (after 26 to 36 weeks of treatment )
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 )
Core Study: Change From Baseline to End of Study in Infarction Segment Length (ISL) as Measured by Echocardiography
Délai: Baseline and final visit (after 26 to 36 weeks of treatment)
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)
Core Study: Change From Baseline to End of Study in Wall Motion Score (WMS) as Measured by Echocardiography
Délai: Baseline and final visit (after 26 to 36 weeks of treatment)
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)
Extension Study: Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 12
Délai: Baseline(extension study), Month 12 (extension study)
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)
Extension Study: Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 12
Délai: Baseline (extension study), Month 12 (extension study)
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)
Extension Study: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 12
Délai: Baseline(extension study), Month 12 (extension study)
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)
Extension Study: Percentage of Participants With Orthostatic Blood Pressure Change
Délai: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24
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
Extension Study: Percentage of Participants With Specified Criteria in Selected Labs by Laboratory Parameter
Délai: 24 Months

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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis

Les enquêteurs

  • Chaise d'étude: Novartis US, Novartis

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 décembre 2006

Achèvement primaire (Réel)

1 septembre 2009

Achèvement de l'étude (Réel)

1 juillet 2011

Dates d'inscription aux études

Première soumission

19 décembre 2006

Première soumission répondant aux critères de contrôle qualité

20 décembre 2006

Première publication (Estimation)

21 décembre 2006

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

13 juillet 2012

Dernière mise à jour soumise répondant aux critères de contrôle qualité

5 juillet 2012

Dernière vérification

1 juillet 2012

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CSPP100A2340

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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