Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension
- Conditions
- Hypertension
- Interventions
- Drug: LCZ696 matching placebo
- Registration Number
- NCT01692301
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 454
- 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 1.
- 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 1.
- All patients must have pulse pressure >60 mmHg at Visit 201. 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 201.
Key
- 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 1.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LCZ696 (sacubitril/valsartan) LCZ696 matching placebo 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. LCZ696 (sacubitril/valsartan) Olmesartan matching placebo 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. LCZ696 (sacubitril/valsartan) amlodipine 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. Olmesartan LCZ696 matching placebo 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. LCZ696 (sacubitril/valsartan) LCZ696 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. LCZ696 (sacubitril/valsartan) hydrochlorothiazide 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. Olmesartan 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. Olmesartan amlodipine 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. Olmesartan hydrochlorothiazide 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks 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.
- Secondary Outcome Measures
Name Time Method 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 Pulse wave velocity recordings were performed on patient while in a supine, face-up position.
Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks baseline, 52 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.Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) baseline, 12 weeks, and 52 weeks At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) baseline, 12 weeks, and 52 weeks At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
Change From Baseline in Mean Sitting Pulse Pressure (msPP) baseline, 12 weeks, and 52 weeks Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
Change From Baseline in Mean Arterial Pressure (MAP) baseline, 12 weeks, and 52 weeks Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 \* msDBP + msSBP)/3.
Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP) Baseline, 12 weeks, and 52 weeks An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP) Baseline, 12 weeks, and 52 weeks An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP) Baseline, 12 weeks, and 52 weeks Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇳Taipei, Taiwan