Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH)

This study has been terminated.

(The study was terminated early because of significant efficacy results for the primary endpoint in favor of benazepril/amlodipine treatment.)

Sponsor:

Information provided by:

Novartis

ClinicalTrials.gov Identifier:

NCT00170950

First received: September 10, 2005

Last updated: April 19, 2011

Last verified: April 2011

History of Changes

Results First Received: January 13, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Hypertension
Interventions:	Drug: Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1 Drug: Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2 Drug: Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter Drug: Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1 Drug: Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2 Drug: Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter

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
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Reporting Groups

	Description
Benazepril/Amlodipine	Benazepril hydrochloride (HCl)/amlodipine besylate: 20/5 mg (Dose Level 1 from Day 1 to Month 1), 40/5 mg (Dose Level 2 from Month 1 to Month 2), and 40/10 mg (Dose Level 3 from Month 2 to Month 3 and thereafter) capsules for oral administration once daily
Benazepril/Hydrochlorothiazide	Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ): 20/12.5 mg (Dose Level 1 from Day 1 to Month 1), 40/12.5 mg (Dose Level 2 from Month 1 to Month 2), and 40/25 mg (Dose Level 3 from Month 2 to Month 3 and thereafter) capsules for oral administration once daily

Participant Flow: Overall Study

	Benazepril/Amlodipine	Benazepril/Hydrochlorothiazide
STARTED	5744	5762
COMPLETED	4859	4852
NOT COMPLETED	885	910
Death	236	274
Withdrawal by Subject	496	498
Lost to Follow-up	134	115
Missing	2	1
Termination Data Not Recorded	17	22

Baseline Characteristics

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Reporting Groups

	Description
Benazepril/Amlodipine	Benazepril hydrochloride (HCl)/amlodipine besylate: 20/5 mg (Dose Level 1 from Day 1 to Month 1), 40/5 mg (Dose Level 2 from Month 1 to Month 2), and 40/10 mg (Dose Level 3 from Month 2 to Month 3 and thereafter) capsules for oral administration once daily
Benazepril/Hydrochlorothiazide	Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ): 20/12.5 mg (Dose Level 1 from Day 1 to Month 1), 40/12.5 mg (Dose Level 2 from Month 1 to Month 2), and 40/25 mg (Dose Level 3 from Month 2 to Month 3 and thereafter) capsules for oral administration once daily
Total	Total of all reporting groups

Baseline Measures

	Benazepril/Amlodipine	Benazepril/Hydrochlorothiazide	Total
Number of Participants [units: participants]	5744	5761	11505
Age ^[1] [units: Years] Mean ± Standard Deviation	68.4 ± 6.86	68.3 ± 6.86	68.4 ± 6.86
Gender ^[1] [units: Participants]
Female	2296	2246	4542
Male	3448	3515	6963

[1]	Demographic data for 1 patient in the benazepril/hydrochlorothiazide was not available.

Outcome Measures

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1. Primary:

Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event [ Time Frame: For each patient, baseline to time of first CV morbidity or mortality event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.]) ]

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2. Secondary:

Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event [ Time Frame: For each patient, baseline to time of first CV morbidity event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])] ]

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3. Secondary:

Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke [ Time Frame: For each patient, baseline to time of first CV mortality event, MI (non-fatal), or stroke (non-fatal) (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.]) ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	Double-blind period
Additional Description	Safety population includes all randomized patients who took at least one dose of study medication by actual treatment group (7 Benazepril / Amlodipine and 2 Benazepril / HCTZ patients did not take study medication; 3 patients assigned to Benazepril / HCTZ received Benazepril / Amlodipine medication instead).

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Benazepril / Amlodipine	Benazepril hydrochloride (HCl)/amlodipine besylate: 20/5 mg (Dose Level 1), 40/5 mg (Dose Level 2), and 40/10 mg (Dose Level 3) capsules for oral administration once daily
Benazepril / HCTZ	Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ): 20/12.5 mg (Dose Level 1), 40/12.5 mg (Dose Level 2), and 40/25 mg (Dose Level 3) capsules for oral administration once daily

Other Adverse Events

	Benazepril / Amlodipine	Benazepril / HCTZ
Total, other (not including serious) adverse events
# participants affected / at risk	3077/5740	2663/5757
General disorders
Oedema peripheral ^{† 1}
# participants affected / at risk	1787/5740 (31.13%)	768/5757 (13.34%)
Nervous system disorders
Dizziness ^{† 1}
# participants affected / at risk	1175/5740 (20.47%)	1440/5757 (25.01%)
Respiratory, thoracic and mediastinal disorders
Cough ^{† 1}
# participants affected / at risk	1172/5740 (20.42%)	1217/5757 (21.14%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA

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 its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the 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
Study was stopped early, as recommended by the Data Monitoring Committee, due to positive efficacy results.

Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862 778-8300

Publications of Results:

Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, Hester A, Gupte J, Gatlin M, Velazquez EJ; ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008 Dec 4;359(23):2417-28.

Publications automatically indexed to this study:

Weber MA, Jamerson K, Bakris GL, Weir MR, Zappe D, Zhang Y, Dahlof B, Velazquez EJ, Pitt B. Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial. Lancet. 2013 Feb 16;381(9866):537-45. doi: 10.1016/S0140-6736(12)61343-9. Epub 2012 Dec 6.

Weber MA, Bakris GL, Jamerson K, Weir M, Kjeldsen SE, Devereux RB, Velazquez EJ, Dahlöf B, Kelly RY, Hua TA, Hester A, Pitt B; ACCOMPLISH Investigators. Cardiovascular events during differing hypertension therapies in patients with diabetes. J Am Coll Cardiol. 2010 Jun 29;56(1):77-85.

Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, Velazquez EJ, Staikos-Byrne L, Kelly RY, Shi V, Chiang YT, Weber MA; ACCOMPLISH Trial investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010 Apr 3;375(9721):1173-81. Epub 2010 Feb 18.

Responsible Party:	Study Diorector, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00170950 History of Changes
Obsolete Identifiers:	NCT00097864
Other Study ID Numbers:	CCIB002I2301
Study First Received:	September 10, 2005
Results First Received:	January 13, 2011
Last Updated:	April 19, 2011
Health Authority:	United States: Food and Drug Administration

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