Clinical trial NCT00170950: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension
Official title: A Prospective, Multinational, Multicenter Trial to Compare the Effects of Amlodipine/Benazepril to Benazepril and Hydrochlorothiazide Combined on the Reduction of Cardiovascular Morbidity and Mortality in Patients With High Risk Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypertension
Keywords: cardiovascular morbidity
cardiovascular mortality
benazepril
amlodipine
high risk population
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 11506
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A comparison study of two combination drugs, amlodipine/benazepril and benazepril/HCTZ to evaluate the effectiveness of the combination on reducing heart disease and death in a high risk hypertensive population.


Eligibility criteria: Inclusion Criteria:

* At least 55 years of age.
* Previously untreated or treated hypertension.
* For patients \>= 60 years, evidence of at least one CV disease or target organ damage, or for patients 55-59 years evidence of at least two CV diseases or target organ damage from two different organ systems as defined in the protocol.

Exclusion Criteria:

* Allergy to any of the drugs administered in this trial.
* Current angina pectoris (ie, no anginal event requiring NTG within 1 month prior to Visit 1).
* Secondary hypertension.
* Refractory hypertension defined as SBP \>= 180 mmHg and/or DBP \>= 110 mmHg unresponsive to triple-drug regimens of sympatholytics, diuretics and vasodilators.
* History of symptomatic heart failure (NYHA classes II-IV) or ejection fraction \< 40%.
* Myocardial infarction, coronary revascularization (CABG or PCI), unstable angina within one month of Visit 1.
* Stroke or transient ischemic event (TIA) within 3 months of Visit 1.
* Significant obstructive valvular cardiovascular disease or any valvular disease expected to lead to surgery during the course of the study.
* Evidence of hepatic disease (AST or ALT values \>= 2 X upper limit of normal).
* Impaired renal function (serum creatinine \>= 2.5 mg/dL (221 µmol/L)).
* Baseline serum potassium of \> 5.2 meq/L not on potassium supplements.
* History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the last 5 years.
* History of clinically significant auto immune disorders such as Systemic Lupus Erythematosus.
* Significant non-cardiovascular illness or condition likely to result in death prior to trial completion, e.g., major organ transplant (life expectancy \<5 years).
* Significant cardiovascular disease such as an aortic aneurysm ≥ 6 cm, likely requiring surgical intervention during the course of the study.

Other protocol-defined exclusion criteria applied to the study.

Primary outcomes:
measure: Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event
timeFrame: 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.])
Secondary outcomes:
measure: Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event
timeFrame: 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.])]
measure: Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke
timeFrame: 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.])
Other outcomes:
Locations:
city: East Hanover
country: United States
facility: Novartis Pharmaceuticals
state: New Jersey
city: Denmark
country: Denmark
facility: sites in Denmark
city: Finland
country: Finland
facility: sites in Finland
city: Norway
country: Norway
facility: sites in Norway
city: Sweden
country: Sweden
facility: sites in Sweden
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_CHAIR
References:
citation: Jamerson K, Weber MA, Bakris GL, Dahlof 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. doi: 10.1056/NEJMoa0806182.
citation: Brook RD, Kaciroti N, Bakris G, Dahlof B, Pitt B, Velazquez E, Weber MA, Jamerson KA. Cardiovascular Benefits of Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade in Patients Achieving Tight Blood Pressure Control and With Resistant Hypertension. Am J Hypertens. 2021 May 22;34(5):531-539. doi: 10.1093/ajh/hpaa192.
citation: 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.
citation: Weber MA, Bakris GL, Jamerson K, Weir M, Kjeldsen SE, Devereux RB, Velazquez EJ, Dahlof 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. doi: 10.1016/j.jacc.2010.02.046.
citation: Bakris GL, Sarafidis PA, Weir MR, Dahlof 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. doi: 10.1016/S0140-6736(09)62100-0. Epub 2010 Feb 18.