A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People "APOLLO"

Terminated

Phase 3 Results

Trial Description

This study was planned to provide new information regarding the role of aliskiren (with or without additional therapy with a diuretic or a Calcium channel blockers (CCB)) in elderly individuals (≥ 65 years) with systolic blood pressure (SBP) 130 to 159 mmHg, in preventing major cardiovascular (CV) events and on global measures of physical, executive and cognitive function.

Detailed Description

This was 2x2 factorial design study with 2 strata. As per protocol, the first co- Primary analysis as well as secondary analysis were aliskiren based regimen vs non-aliskiren based regimen. All aliskiren based arm were combined into the aliskiren based regimen and all non-aliskiren based arms were combined into non-aliskiren based regimen.

Trial Stopped: Terminated early in agreement with Health Authorities for feasibility reasons

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: Placebo
    ARM 1: Kind: Experimental
    Label: Double placebo
    Description: Placebo to Aliskeren Placebo to Comparator
  • Amlodipine Drug
    Intervention Desc: Amlodipine 5 mg
    ARM 1: Kind: Experimental
    Label: Aliskiren + Amlodipine
    Description: In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.
    ARM 2: Kind: Experimental
    Label: Amlodipine + Placebo for Aliskiren
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily
  • Aliskiren Drug
    Other Names: Tekturna
    Intervention Desc: Aliskiren 150/300 mg once daily
    ARM 1: Kind: Experimental
    Label: Aliskiren monotherapy
    Description: Aliskiren
    ARM 2: Kind: Experimental
    Label: Aliskiren + Amlodipine
    Description: In run-in period (4-5 weeks) , patients on thiazide background therapy and approximately 50% of patients on neither CCB nor thiazide background therapy received Amlodipine 5 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.
    ARM 3: Kind: Experimental
    Label: Aliskiren + Hydrochlorothiazide (HCTZ)
    Description: In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received Hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.
    ARM 4: Kind: Experimental
    Label: Aliskiren + Placebo for Amlodipine
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for Amlodipine 5 mg
    ARM 5: Kind: Experimental
    Label: Aliskiren + Placebo for HCTZ
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for HCTZ 25 mg once daily
  • Aliskiren and Amlodipine or HCTZ Drug
    Intervention Desc: Aliskiren and Amlodipine or HCTZ
    ARM 1: Kind: Experimental
    Label: Aliskiren combination
    Description: Aliskiren and Amlodipine or HCTZ
  • Amlodipine or HCTZ Drug
    Intervention Desc: Amlodipine or HCTZ
    ARM 1: Kind: Experimental
    Label: Comparator monotherapy
    Description: Amlodipine or HCTZ
  • Hydrochlorothiazide (HCTZ) Drug
    Intervention Desc: HCTZ 12.5/25 mg
    ARM 1: Kind: Experimental
    Label: Aliskiren + Hydrochlorothiazide (HCTZ)
    Description: In run-in period (4-5 weeks) , patients on CCB background therapy and approximately 50% of patients on neither thiazide nor CCB background therapy: received Hydrochlorothiazide 12.5/25 mg and Aliskiren 150/300 mg daily in a titrated manner as per protocol. In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily.
    ARM 2: Kind: Experimental
    Label: HCTZ + Placebo for Aliskiren
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily
  • Placebo for Aliskiren Drug
    Intervention Desc: Placebo for Aliskiren 300 mg
    ARM 1: Kind: Experimental
    Label: Amlodipine + Placebo for Aliskiren
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily
    ARM 2: Kind: Experimental
    Label: HCTZ + Placebo for Aliskiren
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily
    ARM 3: Kind: Experimental
    Label: Placebo for Aliskiren + Placebo for Amlodipine
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
    ARM 4: Kind: Experimental
    Label: Placebo for Aliskiren + Placebo for HCTZ
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily
  • Placebo for Amlodipine Drug
    Intervention Desc: Placebo for Amlodipine
    ARM 1: Kind: Experimental
    Label: Aliskiren + Placebo for Amlodipine
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for Amlodipine 5 mg
    ARM 2: Kind: Experimental
    Label: Placebo for Aliskiren + Placebo for Amlodipine
    Description: In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily
  • Placebo for Hydrochlorothiazide (HCTZ) Drug
    Intervention Desc: Placebo for HCTZ 12.5/25 mg
    ARM 1: Kind: Experimental
    Label: Aliskiren + Placebo for HCTZ
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received Aliskiren 300 mg + Placebo for HCTZ 25 mg once daily
    ARM 2: Kind: Experimental
    Label: Placebo for Aliskiren + Placebo for HCTZ
    Description: In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum. In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Factorial Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Reduction in risk of major cardiovascular events (composite of CV death, non-fatal MI, non-fatal stroke and significant heart failure) 6 years Yes
Secondary Prevention of decline in the ability to perform everyday activities independently 6 years Yes
Secondary Prevention of decline in renal function. 6 years Yes
Secondary Reduction of total mortality 6 years Yes
Primary Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen End of study (209 days (median)) No
Primary Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group End of study (209 days (median)) No
Secondary Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) Baseline, End of study (209 days [median]) No
Secondary Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) End of study (209 days [median]) No
Secondary Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen End of study (209 days (median)) No
Secondary Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen End of study (209 days (median)) Yes

Sponsors