A Randomized, Double-blind 52-week Study to Evaluate the Safety and Efficacy of an LCZ696 Regimen Compared to an Olmesartan Regimen on Arterial Stiffness Through Assessment of Central Blood Pressure in Elderly Patients With Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 454
- 试验地点
- 1
- 主要终点
- Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
研究概览
简要总结
The study examined the efficacy of LCZ696 in comparison to the ARB olmesartan on Central Aortic Systolic Blood Pressure (CASP) and other measures of central hemodynamics and arterial stiffness in elderly patients with an elevated systolic blood pressure (SBP) and widened pulse pressure (PP).
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients ≥ 60 years of age.
- •Patients with essential hypertension, untreated or currently taking antihypertensive therapy.
- •Untreated patients must have an office msSBP ≥150 mmHg and <180 mmHg at Visit 101 and Visit 201 if they are newly diagnosed or have not been treated with antihypertensive drugs for the 4 weeks prior to Visit
- •Treated patients must have an office msSBP ≥140 mmHg and <180 mmHg at Visit 102 (or Visit 103) and msSBP ≥150 mmHg and <180 mmHg at Visit 201 if they have been treated with antihypertensive drugs for the 4 weeks prior to Visit
- •All patients must have pulse pressure >60 mmHg at Visit
- •Pulse pressure is defined as msSBP- msDBP.
- •Patients must have a difference in msSBP within +/-15 mmHg between Visit 201 (randomization) and the visit immediately prior to Visit
排除标准
- •Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
- •History of angioedema, drug-related or otherwise.
- •History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension.
- •Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.
- •History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit
- •History of atrial fibrillation or atrial flutter during the 3 months prior to Visit 1, or active atrial fibrillation or atrial flutter on the ECG at screening.
研究组 & 干预措施
LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
干预措施: LCZ696 (Drug)
LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
干预措施: LCZ696 matching placebo (Drug)
LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
干预措施: Olmesartan matching placebo (Drug)
LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
干预措施: amlodipine (Drug)
LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
干预措施: hydrochlorothiazide (Drug)
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
干预措施: Olmesartan (Drug)
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
干预措施: LCZ696 matching placebo (Drug)
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
干预措施: amlodipine (Drug)
Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
干预措施: hydrochlorothiazide (Drug)
结局指标
主要结局
Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
时间窗: baseline, 12 weeks
Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software. At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
次要结局
- Change From Baseline in Mean Central Pulse (CPP) Pressure(Baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean Pulse Wave Velocity (PWV)(baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks(baseline, 52 weeks)
- Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)(baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)(baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean Sitting Pulse Pressure (msPP)(baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean Arterial Pressure (MAP)(baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)(Baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)(Baseline, 12 weeks, and 52 weeks)
- Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)(Baseline, 12 weeks, and 52 weeks)