A Twelve Week, Randomized, Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren/Ramipril/Amlodipine (300/10/5-10 mg) Compared to the Combinations of Ramipril/Amlodipine (10/5-10 mg) and Aliskiren/Amlodipine (300/5-10 mg) in Patients With Essential Hypertension and Metabolic Syndrome Not Adequately Responsive to Amlodipine 5-10 mg
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- Novartis
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine)
研究概览
简要总结
This proof of concept study is designed to evaluate the efficacy and safety of the combination therapy of aliskiren and ramipril as add-on to amlodipine in the treatment of patients with essential hypertension and metabolic syndrome who do not respond adequately to amlodipine monotherapy.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatients 18-75 years of age.
- •Male or female patients are eligible.
- •Patients with a diagnosis of hypertension:
- •Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a mean sitting systolic blood pressure (MSSBP) > 150 mmHg and < 180 mmHg at Visit
- •Patients treated with antihypertensive monotherapy must have a MSSBP ≥ 140 mmHg and <180 mmHg at Visit
- •Patients taking amlodipine monotherapy MSSBP > 140 mmHg and < 180 mmHg at visit
- •All patients must have a MSSBP ≥ 140 mmHg and < 180 mmHg at Visit 3, the end of the amlodipine run-in period.
- •Metabolic syndrome.
- •Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written inform consent form).
排除标准
- •Severe hypertension (office cuff MSDBP ≥ 115 mmHg and/or MSSBP ≥ 180 mmHg).
- •History or evidence of a secondary form of hypertension.
- •History of hypertensive encephalopathy or cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
- •Serum sodium < 135 mmol/L at Visit 1 if confirmed on repeat sample.
- •Serum potassium < 3.5 mmol/L or ≥ 5.3 mmol/L at Visit 1, if confirmed on repeat sample.
- •Type 1 diabetes mellitus.
- •Type 2 diabetes if oral hypoglycaemic therapy changed (dose change or medication change) in previous 3 months.
- •Pregnant or nursing (lactating) women.
- •Other protocol-defined inclusion/exclusion criteria applied to the study.
研究组 & 干预措施
Aliskiren / ramipril / amlodipine
6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Amlodipine (Drug)
Aliskiren / ramipril / amlodipine
6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Aliskiren (Drug)
Aliskiren / ramipril / amlodipine
6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Ramipril (Drug)
Aliskiren / amlodipine
6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg placebo capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg placebo capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Amlodipine (Drug)
Aliskiren / amlodipine
6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg placebo capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg placebo capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Aliskiren (Drug)
Ramipril / amlodipine
6 weeks treatment with aliskiren 150 mg placebo tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg placebo tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Amlodipine (Drug)
Ramipril / amlodipine
6 weeks treatment with aliskiren 150 mg placebo tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg placebo tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
干预措施: Ramipril (Drug)
结局指标
主要结局
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine)
时间窗: Baseline to Week 12
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine
时间窗: Baseline to Week 12
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.
次要结局
- Change in HbA1c (Glycated Hemoglobin) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine)(Baseline to Week 12)
- Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine(Baseline to Week 12)
- Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine(Baseline to Week 12)
- Percentage of Patients Who Achieved Normalized Blood Pressure at End of Study(Week 12)
- Change in HOMA-IR From Baseline to End of Study(Baseline to Week 12)
- Change in HOMA-β From Baseline to End of Study(Baseline to Week 12)
- Change in HbA1c (Glycated Hemoglobin) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine(Baseline to Week 12)
- Percentage of Patients Who Developed Diabetes at End of Study(Week 12)