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

This study has been terminated.
(Terminated early in agreement with Health Authorities for feasibility reasons)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01259297
First received: December 10, 2010
Last updated: February 27, 2014
Last verified: February 2014
Results First Received: December 18, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cardiovascular Events
Interventions: Drug: Aliskiren
Drug: Amlodipine
Drug: Hydrochlorothiazide (HCTZ)
Drug: Placebo for Aliskiren
Drug: Placebo for Amlodipine
Drug: Placebo for Hydrochlorothiazide (HCTZ)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Aliskiren + Hydrochlorothiazide (HCTZ)

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.

Aliskiren + Placebo for HCTZ

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 + Amlodipine

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.

Aliskiren + Placebo for Amlodipine

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

HCTZ + Placebo for Aliskiren

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 + Placebo for HCTZ

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

Amlodipine + Placebo for Aliskiren

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

Placebo for Aliskiren + Placebo for Amlodipine

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


Participant Flow for 2 periods

Period 1:   Run-in Open Label Period (4-5 Weeks)
    Aliskiren + Hydrochlorothiazide (HCTZ)     Aliskiren + Placebo for HCTZ     Aliskiren + Amlodipine     Aliskiren + Placebo for Amlodipine     HCTZ + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for HCTZ     Amlodipine + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for Amlodipine  
STARTED     1335     0     1001     0     0     0     0     0  
COMPLETED     980     0     779     0     0     0     0     0  
NOT COMPLETED     355     0     222     0     0     0     0     0  

Period 2:   Double Blind Randomized Period
    Aliskiren + Hydrochlorothiazide (HCTZ)     Aliskiren + Placebo for HCTZ     Aliskiren + Amlodipine     Aliskiren + Placebo for Amlodipine     HCTZ + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for HCTZ     Amlodipine + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for Amlodipine  
STARTED     244     232     189     195     251     253     196     199  
COMPLETED     242     229     188     191     247     245     190     196  
NOT COMPLETED     2     3     1     4     4     8     6     3  
Death                 1                 1                 1                 2                 1                 5                 2                 1  
Withdrew informed consent/ refused visit                 1                 1                 0                 2                 2                 1                 1                 1  
Other reasons                 0                 1                 0                 0                 1                 2                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis Set (FAS): All randomized patients, regardless of receiving study medication.

Reporting Groups
  Description
Aliskiren + Hydrochlorothiazide (HCTZ)

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.

Aliskiren + Placebo for HCTZ

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 + Amlodipine

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.

Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period.

Aliskiren + Placebo for Amlodipine

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

HCTZ + Placebo for Aliskiren

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 + Placebo for HCTZ

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

Amlodipine + Placebo for Aliskiren

In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were run-in stratum 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

Placebo for Aliskiren + Placebo for Amlodipine

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

Total Total of all reporting groups

Baseline Measures
    Aliskiren + Hydrochlorothiazide (HCTZ)     Aliskiren + Placebo for HCTZ     Aliskiren + Amlodipine     Aliskiren + Placebo for Amlodipine     HCTZ + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for HCTZ     Amlodipine + Placebo for Aliskiren     Placebo for Aliskiren + Placebo for Amlodipine     Total  
Number of Participants  
[units: participants]
  244     232     189     195     251     253     196     199     1759  
Age, Customized  
[units: participants]
                 
>=65 to <75 years     165     174     127     125     180     189     135     134     1229  
>=75 years     79     58     62     70     71     64     61     65     530  
Gender  
[units: participants]
                 
Female     119     109     91     89     122     108     87     88     813  
Male     125     123     98     106     129     145     109     111     946  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen   [ Time Frame: End of study (209 days (median)) ]

2.  Primary:   Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group   [ Time Frame: End of study (209 days (median)) ]

3.  Secondary:   Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)   [ Time Frame: Baseline, End of study (209 days [median]) ]

4.  Secondary:   Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)   [ Time Frame: End of study (209 days [median]) ]

5.  Secondary:   Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen   [ Time Frame: End of study (209 days (median)) ]

6.  Secondary:   Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen   [ Time Frame: End of study (209 days (median)) ]

7.  Other Pre-specified:   Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline (BL), 6 week, 6 month and 12 month ]

8.  Other Pre-specified:   Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline (BL), 6 week, 6 month and 12 month ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Due to early termination, 1759 patients were randomized as against 11,000. Only 25 primary endpoints had accrued during median follow-up of 209 days as against planned 2000 in 5 years. These low numbers significantly limit interpretation of results.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01259297     History of Changes
Other Study ID Numbers: CSPP100G2301, 2009-010170-38
Study First Received: December 10, 2010
Results First Received: December 18, 2013
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: Ministry of Health
Canada: Health Canada
Chile: Ministry of Health
China: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Ireland: Ministry of Health
Israel: Ministry of Health
Italy: National Institute of Health
Malaysia: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Philippines: Bureau of Food and Drugs (BFAD)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Turkey: Ministry of Health