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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Novartis
- 入组人数
- 11,506
- 试验地点
- 5
- 主要终点
- Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Stroke or transient ischemic event (TIA) within 3 months of Visit
- •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.
研究组 & 干预措施
Benazepril/amlodipine
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.
干预措施: Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1 (Drug)
Benazepril/amlodipine
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.
干预措施: Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2 (Drug)
Benazepril/amlodipine
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.
干预措施: Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter (Drug)
Benazepril/hydrochlorothiazide
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.
干预措施: Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1 (Drug)
Benazepril/hydrochlorothiazide
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.
干预措施: Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2 (Drug)
Benazepril/hydrochlorothiazide
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.
干预措施: Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter (Drug)
结局指标
主要结局
Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event
时间窗: 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.
次要结局
- 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.]))
- 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.])])