An 8 Week Randomized, Double-Blind, Parallel Group, Multi-Center, Active Controlled Study to Evaluate the Antihypertensive Efficacy and Safety of Aliskiren Administered in Combination With Valsartan Versus Valsartan Alone in Patients With Stage 2 Systolic Hypertension and Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 1,143
- 试验地点
- 1
- 主要终点
- Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8
研究概览
简要总结
The purpose of the study was to evaluate the blood pressure (BP)-lowering efficacy of the combination of aliskiren and valsartan, as initial therapy, compared to valsartan monotherapy in Type II Diabetic patients with Stage II hypertension.
详细描述
When protocol Amendment 2 was released, there were patients who had already been randomized into the study. These patients were included in the trial prior to making changes to the eligibility criteria. Thus, the study contains 2 distinct cohorts. Cohort 1 contains those patients who had already been randomized, and had been deemed eligible based on the original inclusion/exclusion criteria, prior to Amendment 2. No new patients were randomized to Cohort 1. Cohort 2 contains patients who were randomized, having been found eligible based on the revised inclusion/exclusion criteria, after Amendment 2. Differences in the inclusion and exclusion criteria are indicated below.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed.
- •Men or women 18 years and older.
- •Patients with Type 2 diabetes mellitus with an HbA1c ≤ 9 % at visit 1 and on a stable anti-diabetic regimen not including insulin or stable diet and exercise for at least 4 weeks prior to visit
- •Patients with Stage 2 systolic hypertension, defined as having a MSSBP ≥160 mmHg and <200 mmHg at Visit 5 (randomization).
- •Patients who have been newly diagnosed with hypertension or who have not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have MSSBP ≥ 160 mmHg and < 200 mmHg at Visit 1, otherwise, they will be considered screen failures.
- •Patients receiving antihypertensive medication must have a MSSBP of ≥150 mmHg and <200 mmHg at Study Visit 1, otherwise they will be considered screen failures.
- •Patients must also have had a mean 8-hour daytime ambulatory systolic blood pressure (ASBP) ≥140 mmHg AND mean 8-hour daytime ambulatory diastolic blood pressure (ADBP) ≥90 mmHg at Visit 5 (randomization).
- •Hypertensive patients with MSSBP ≥150 mmHg and but <200 mmHg AND MSDBP ≥95 but <120 mmHg at Visit 5 (randomization).
- •Patients who had been newly diagnosed with hypertension or who had not received antihypertensive medication for at least 4 weeks (28 days) prior to Visit 1 must have had MSSBP ≥150 mmHg but <200 mmHg and MSDBP ≥95 but <120 mmHg at Visit 1, otherwise, they were considered screen failures.
排除标准
- •Office blood pressure measured by cuff (MSSBP ≥200 mmHg or MSDBP ≥120 mmHg).
- •History or evidence of secondary hypertension of any etiology.
- •Refractory hypertension, defined as having uncontrolled BP (≥140/90 mmHg) while receiving 3 antihypertensive medications at the maximum approved dose of each drug, one of which must be a diuretic.
- •Patients treated with more than 3 antihypertensive medications (each component of a combination drug counts individually).
- •Type 2 diabetes mellitus currently requiring insulin treatment.
- •modification of diet in renal disease (MDRD) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2
- •Serum sodium less than lower limit of normal, serum potassium < 3.5 mEq/L or ≥ 5.3 mEq/L at Visit
- •Known Keith-Wagener grade III or IV hypertensive retinopathy.
- •Patients with known diabetic retinopathy (eg, having a history of laser therapy for diabetic retinopathy) or diabetic neuropathy (eg, receiving medication for diabetic neuropathy).
- •Patients with known diabetic retinopathy or diabetic neuropathy and/or having a history of treatment for either.
- •Other protocol-defined inclusion/exclusion criteria applied.
研究组 & 干预措施
Combination Therapy: Aliskiren + Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day)for 8 weeks. 1 tablet of Aliskiren 150 mg + 1 tablet of placebo Aliskiren 150 mg + 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg daily for 2 weeks. Forced titrated to: 2 tablets of Aliskiren 150 mg + 2 capsules of Valsartan 160 mg daily for 6 weeks
干预措施: Aliskiren (Drug)
Combination Therapy: Aliskiren + Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day)for 8 weeks. 1 tablet of Aliskiren 150 mg + 1 tablet of placebo Aliskiren 150 mg + 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg daily for 2 weeks. Forced titrated to: 2 tablets of Aliskiren 150 mg + 2 capsules of Valsartan 160 mg daily for 6 weeks
干预措施: Valsartan (Drug)
Combination Therapy: Aliskiren + Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day)for 8 weeks. 1 tablet of Aliskiren 150 mg + 1 tablet of placebo Aliskiren 150 mg + 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg daily for 2 weeks. Forced titrated to: 2 tablets of Aliskiren 150 mg + 2 capsules of Valsartan 160 mg daily for 6 weeks
干预措施: Placebo for Aliskiren (Drug)
Combination Therapy: Aliskiren + Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day)for 8 weeks. 1 tablet of Aliskiren 150 mg + 1 tablet of placebo Aliskiren 150 mg + 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg daily for 2 weeks. Forced titrated to: 2 tablets of Aliskiren 150 mg + 2 capsules of Valsartan 160 mg daily for 6 weeks
干预措施: Placebo for Valsartan (Drug)
Monotherapy: Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day) for 8 weeks. 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 2 weeks. Forced titrated to: 2 capsules of Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 6 weeks.
干预措施: Valsartan (Drug)
Monotherapy: Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day) for 8 weeks. 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 2 weeks. Forced titrated to: 2 capsules of Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 6 weeks.
干预措施: Placebo for Aliskiren (Drug)
Monotherapy: Valsartan
To adequately blind the study, patients were required to take a total of 4 tablets/capsules a day (2 tablets and 2 capsules of study drug per day) for 8 weeks. 1 capsule of Valsartan 160 mg + 1 capsule of placebo Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 2 weeks. Forced titrated to: 2 capsules of Valsartan 160 mg + 2 tablets of placebo Aliskiren 150 mg daily for 6 weeks.
干预措施: Placebo for Valsartan (Drug)
结局指标
主要结局
Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (MASBP) at Week 8
时间窗: baseline, week 8
The 24-hour ambulatory systolic blood pressure was evaluated at baseline (Week 0) and post-baseline visits. The mean hourly systolic blood pressure was calculated at post-dosing hours 1-24 for each patient. The MASBP for each patient was calculated by averaging the patient's available hourly means for post-dosing hours 1-24.
次要结局
- Change From Baseline in Mean Sitting Systolic Blood Pressure (MSSBP)(Baseline, week 8)
- Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (MADBP) at Week 8(baseline, week 8)
- Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (MAPP) at Week 8(baseline, week 8)
- Change From Baseline in Mean Sitting Diastolic Blood Pressure (MSDBP)(Baseline, week 8)
- Change From Baseline in Mean Sitting Pulse Pressure (MSPP) at Week 8(baseline, week 8)
- Percentage of Patients Achieving Blood Pressure Control(8 weeks)
- Percentage of Responders(Baseline, Week 8)
- Change From Baseline in Plasma Renin Activity (PRA) at Week 8(Baseline, week 8)
- Change From Baseline in Plasma Renin Concentration (PRC) at Week 8(Baseline, week 8)
- Change From Baseline in Plasma Aldosterone at Week 8(Baseline, week 8)
- Number of Patients With Adverse Events, Serious Adverse Events and Death(8 weeks)