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Aliskiren and the Calcium Channel Blocker Amlodipine Combination as an Initial Treatment Strategy for Hypertension (ACCELERATE)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00797862
First received: November 24, 2008
Last updated: October 7, 2011
Last verified: June 2011
Results First Received: April 21, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Diagnostic
Condition: Hypertension
Interventions: Drug: Amlodipine
Drug: hydrochlorothiazide
Drug: Aliskiren

  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
A 2-4 week single-blind placebo run in. 7 patients were assigned a randomization number in error (3 each in the aliskiren/amlodipine initial treatment and aliskiren based add-on regimens and 1 in the amlodipine based add-on regimen). These patients did not take any double-blind study medication and were excluded from the Full Analysis Set (FAS).

Reporting Groups
  Description
Aliskiren+Amlodipine Eligible participants received oral aliskiren 150 mg + amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of the combination treatment increased to aliskiren 300 mg + amlodipine 10 mg daily. From week 16-24, participants in this group continued combination treatment (aliskiren 300 mg + amlodipine 10 mg) for 8 weeks. At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Aliskiren Start-Amlodipine Add On Eligible participants received oral aliskiren 150 mg daily from week 1-8. From week 8 - 16, the dose of aliskiren increased to 300 mg daily. From week 16-24, amlodipine 10 mg was added to the aliskiren 300 mg for 8 weeks (aliskiren 300 mg + amlodipine 10 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Amlodipine Start-Aliskiren Add On Eligible participants received oral amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of amlodipine increased to 10 mg daily. From week 16-24, aliskiren 300 mg was added to the amlodipine 10 mg for 8 weeks (amlodipine 10 mg + aliskiren 300 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure > 140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (amlodipine 10 mg + aliskiren 300 mg) for an additional 8 weeks. Total treatment period =32 weeks.

Participant Flow:   Overall Study
    Aliskiren+Amlodipine     Aliskiren Start-Amlodipine Add On     Amlodipine Start-Aliskiren Add On  
STARTED     620 [1]   318 [2]   316 [3]
Entered Double-Blind Treatment (FAS)     617     315     315  
COMPLETED     496     250     230  
NOT COMPLETED     124     68     86  
Adverse Event                 86                 44                 58  
Abnormal Test Procedure Result                 0                 1                 1  
Lack of Efficacy                 1                 7                 6  
No longer required study medication                 1                 0                 0  
Withdrawal by Subject                 14                 7                 7  
Lost to Follow-up                 11                 0                 5  
Administrative Problem                 4                 0                 0  
Protocol Violation                 4                 6                 8  
Mis-randomized                 3                 3                 1  
[1] 3 participants were mis-randomized and discontinued. Only 617 participants received study drug.
[2] 3 participants were mis-randomized and discontinued. Only 315 participants received study drug.
[3] 1 participant was mis-randomized and discontinued. Only 315 participants received study drug.



  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.
No text entered.

Reporting Groups
  Description
Aliskiren+Amlodipine Eligible participants received oral aliskiren 150 mg + amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of the combination treatment increased to aliskiren 300 mg + amlodipine 10 mg daily. From week 16-24, participants in this group continued combination treatment (aliskiren 300 mg + amlodipine 10 mg) for 8 weeks. At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Aliskiren Start-Amlodipine Add On Eligible participants received oral aliskiren 150 mg daily from week 1-8. From week 8 - 16, the dose of aliskiren increased to 300 mg daily. From week 16-24, amlodipine 10 mg was added to the aliskiren 300 mg for 8 weeks (aliskiren 300 mg + amlodipine 10 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Amlodipine Start-Aliskiren Add On Eligible participants received oral amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of amlodipine increased to 10 mg daily. From week 16-24, aliskiren 300 mg was added to the amlodipine 10 mg for 8 weeks (amlodipine 10 mg + aliskiren 300 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure > 140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (amlodipine 10 mg + aliskiren 300 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Total Total of all reporting groups

Baseline Measures
    Aliskiren+Amlodipine     Aliskiren Start-Amlodipine Add On     Amlodipine Start-Aliskiren Add On     Total  
Number of Participants  
[units: participants]
  620     318     316     1254  
Age  
[units: years]
Mean ± Standard Deviation
  58.1  ± 10.81     58.4  ± 10.83     58.1  ± 10.93     58.1  ± 10.84  
Gender  
[units: participants]
       
Female     305     154     160     619  
Male     315     164     156     635  



  Outcome Measures
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1.  Primary:   Overall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks   [ Time Frame: Baseline, 8 weeks, 16 weeks, and 24 weeks ]

2.  Primary:   Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24   [ Time Frame: Baseline to 24 weeks ]

3.  Secondary:   Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32   [ Time Frame: Baseline to 32 weeks ]

4.  Secondary:   Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks   [ Time Frame: Baseline, 8 weeks, 16 weeks and 24 weeks ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks
Measure Description Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msDBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures ANCOVA model with treatment, visit and regions as factors, treatment by visit interaction and baseline msDBP as a covariate.
Time Frame Baseline, 8 weeks, 16 weeks and 24 weeks  
Safety Issue No  

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.
The analysis population included participants in the Full Analysis Set, (randomized participants who received at least one dose of study drug) for whom efficacy data was available for this outcome measure.

Reporting Groups
  Description
Aliskiren+Amlodipine Eligible participants received oral aliskiren 150 mg + amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of the combination treatment increased to aliskiren 300 mg + amlodipine 10 mg daily. From week 16-24, participants in this group continued combination treatment (aliskiren 300 mg + amlodipine 10 mg) for 8 weeks. At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Aliskiren Start-Amlodipine Add On Eligible participants received oral aliskiren 150 mg daily from week 1-8. From week 8 - 16, the dose of aliskiren increased to 300 mg daily. From week 16-24, amlodipine 10 mg was added to the aliskiren 300 mg for 8 weeks (aliskiren 300 mg + amlodipine 10 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks.
Amlodipine Start-Aliskiren Add On Eligible participants received oral amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of amlodipine increased to 10 mg daily. From week 16-24, aliskiren 300 mg was added to the amlodipine 10 mg for 8 weeks (amlodipine 10 mg + aliskiren 300 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure > 140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (amlodipine 10 mg + aliskiren 300 mg) for an additional 8 weeks. Total treatment period =32 weeks.

Measured Values
    Aliskiren+Amlodipine     Aliskiren Start-Amlodipine Add On     Amlodipine Start-Aliskiren Add On  
Number of Participants Analyzed  
[units: participants]
  604     312     313  
Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks  
[units: mmHg]
Least Squares Mean ± Standard Error
  -12.39  ± 0.247     -8.37  ± 0.340     -9.02  ± 0.347  

No statistical analysis provided for Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks



5.  Secondary:   Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24   [ Time Frame: Baseline to 24 weeks ]

6.  Secondary:   Percentage of Participants Achieving Overall Blood Pressure Control at 8, 16, 24 and 32 Weeks Endpoints   [ Time Frame: Baseline to week 8, 16, 24 and 32 endpoints ]

7.  Post-Hoc:   Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 32   [ Time Frame: Baseline to 32 weeks ]


  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
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  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


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00797862     History of Changes
Other Study ID Numbers: CSPA100A2307
Study First Received: November 24, 2008
Results First Received: April 21, 2011
Last Updated: October 7, 2011
Health Authority: Canada: Health Canada
Costa Rica: Ministry of Health Costa Rica
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Greece: National Organization of Medicines
South Africa: Medicines Control Council
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Ministry of Health and Social Development