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

Phase 3

Terminated

• Conditions: Hypertension
• Interventions: Drug: Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1; Drug: Benazepril/hydrochlorothiazide 20/12.5 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/hydrochlorothiazide 40/12.5 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 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter

• Registration Number: NCT00170950
• Lead Sponsor: Novartis

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-10
• Study First Submitted: 2005-09-10
• Study First Submitted QC: 2005-09-10
• Study First Posted: 2005-09-15
• Primary Completion: 2008-01
• Study Completion: 2008-05
• Results First Submitted: 2011-01-13
• Results First Submitted QC: 2011-04-19
• Results First Posted: 2011-05-17
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-11
• Last Update Posted: 2023-10-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11506

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Benazepril/amlodipine	Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1	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.
Benazepril/amlodipine	Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2	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.
Benazepril/hydrochlorothiazide	Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1	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.
Benazepril/amlodipine	Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter	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.
Benazepril/hydrochlorothiazide	Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2	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.
Benazepril/hydrochlorothiazide	Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter	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.

Primary Outcome Measures

Name	Time	Method
Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event	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.])	CV morbidity was defined as non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina, resuscitated sudden death, or coronary revascularization procedure. CV mortality was defined as death due to MI, stroke, coronary intervention, congestive heart failure (CHF), sudden cardiac death, or other CV causes.

Secondary Outcome Measures

Name	Time	Method
Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke	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.])	CV mortality was defined as death due to sudden cardiac death, fatal MI, fatal stroke, coronary intervention, congestive heart failure (CHF), or other CV causes.
Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event	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.])]	Cardiovascular morbidity was defined as including any of the following events: non-fatal MI, non-fatal stroke, hospitalization for unstable angina, resuscitated sudden death, or coronary revascularization procedure (PCI or CABG).

Trial Locations

Locations (5)

sites in Denmark; 🇩🇰 Denmark, Denmark

sites in Finland; 🇫🇮 Finland, Finland

Novartis Pharmaceuticals; 🇺🇸 East Hanover, New Jersey, United States

sites in Norway; 🇳🇴 Norway, Norway

sites in Sweden; 🇸🇪 Sweden, Sweden