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

Novartis

Status and phase: Terminated; Phase 3

Conditions: Hypertension

Treatments: Drug: Benazepril/hydrochlorothiazide 40/25 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/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter; Drug: Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2; Drug: Benazepril/amlodipine 20/5 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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00170950

CCIB002I2301

Details and patient eligibility

About

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.

Enrollment: 11,506 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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11,506 participants in 2 patient groups

Benazepril/amlodipine

Experimental group

Description:

Patients were instructed to take one capsule with water in the morning, except on the morning of their next office visit. On office visit days, study medication was taken after completion of the visit evaluations. Following randomization, all patients were treated at Dose Level 1 for 4 weeks, followed by a forced titration to Dose Level 2 for a subsequent 4 week period. Thereafter, patients were titrated as needed to Dose Level 3 to achieve a target blood pressure of \< 140/\< 90 mm Hg. For patients with diabetes or chronic kidney disease, investigators were encouraged to use a target blood pressure of 130/80 mm Hg.

Treatment:

Drug: Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter

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

Benazepril/hydrochlorothiazide

Active Comparator group

Description:

Patients were instructed to take one capsule with water in the morning, except on the morning of their next office visit. On office visit days, study medication was taken after completion of the visit evaluations. Following randomization, all patients were treated at Dose Level 1 for 4 weeks, followed by a forced titration to Dose Level 2 for a subsequent 4 week period. Thereafter, patients were titrated as needed to Dose Level 3 to achieve a target blood pressure of \< 140/\< 90 mm Hg. For patients with diabetes or chronic kidney disease, investigators were encouraged to use a target blood pressure of 130/80 mm Hg.

Treatment:

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

Drug: Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1