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

History of Changes

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
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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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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 ]

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2. Primary:

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

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Measure Type	Primary
Measure Title	Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24
Measure Description	Systolic 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 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region as factors, treatment by visit interaction and baseline msSBP as a covariate.
Time Frame	Baseline to 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
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24 [units: mmHg] Least Squares Mean ± Standard Error	-27.37 ± 0.546	-26.34 ± 0.738	-25.52 ± 0.782

No statistical analysis provided for Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24

3. Secondary:

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

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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 ]

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5. Secondary:

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

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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 ]

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7. Post-Hoc:

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

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The terms and conditions of Novartis' agreements with it's investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until publication of pooled data (i.e., data from all sites) in the clinical trial.

Limitations and Caveats

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
No text entered.

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:

Brown MJ, McInnes GT, Papst CC, Zhang J, MacDonald TM. Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet. 2011 Jan 22;377(9762):312-20. Epub 2011 Jan 12.

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

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