| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01876368 | Efficacy and Safety of LCZ696 Compared to Olmesartan in Essential Hypertensive Patients Not Responsive to Olmesartan | PHASE3 | COMPLETED | 376 | — | — | Sep 1, 2013 | Aug 1, 2014 | Dec 7, 2015 | 51 | United States, Argentina +5 |
| NCT01692301 | Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension | PHASE2 | COMPLETED | 454 | — | — | Dec 1, 2012 | Apr 1, 2015 | May 4, 2016 | 47 | United States, Argentina +10 |
| NCT01631864 | Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects | PHASE2 | COMPLETED | 98 | — | — | Oct 1, 2012 | Jul 1, 2013 | Aug 10, 2015 | 3 | Germany, Netherlands |
| NCT01353508 | Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers | PHASE2 | COMPLETED | 32 | — | — | Mar 1, 2011 | Aug 1, 2012 | Nov 23, 2015 | 1 | Russia |
| NCT01193101 | Efficacy and Safety of LCZ696 Compared to Placebo in Patients With Essential Hypertension | PHASE2 | COMPLETED | 389 | — | — | Aug 1, 2010 | Apr 1, 2011 | Feb 15, 2016 | 34 | China, Japan +3 |
| NCT00549770 | Efficacy and Safety of LCZ696A in Patients With Essential Hypertension | PHASE2 | COMPLETED | 1,334 | — | — | Sep 1, 2007 | Jul 1, 2008 | Aug 25, 2015 | 182 | United States, Argentina +16 |
Twenty-four hour mean ambulatory blood pressure measurements (ABPM) will be performed at baseline and at end of study (week 8). The first 24-hour ABPM will be performed beginning at 24 hours prior to baseline visit and the second will be performed 24 hours prior to week 8 visit.
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.
The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.
Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).
Urine was collected in 12-hour intervals, and of each pooled 24-hour (daily) sample, sodium concentration was measured. The measure type used for this outcome measure (OM) was Geometric Least square Means (LSM).
Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.
| Arm | Type | Description |
|---|---|---|
| LCZ696 200 mg | EXPERIMENTAL | Patients will be treated with one LCZ696 200 mg tablet and one placebo of olmesartan 20 mg capsule once daily for 8 weeks. |
| Olmesartan 20 mg | ACTIVE_COMPARATOR | Patients will be treated with one placebo of LCZ696 200 mg tablet and one olmesartan 20 mg capsule once daily for 8 weeks. |
| LCZ696 (sacubitril/valsartan) | EXPERIMENTAL | 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 | ACTIVE_COMPARATOR | 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 | EXPERIMENTAL | LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks |
| amlodipine | ACTIVE_COMPARATOR | amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks |
| LCZ696 to Valsartan - Heart Failure (HF) cohort | EXPERIMENTAL | Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2. |
| Valsartan to LCZ696 - HF Cohort | EXPERIMENTAL | Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2. |
| LCZ696 to Valsartan - Hypertension (HTN) cohort | EXPERIMENTAL | Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2. |
| Valsartan to LCZ696 - HTN cohort | EXPERIMENTAL | Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2. |
| LCZ696 100 mg | EXPERIMENTAL | LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week. |
| LCZ696 400 mg | EXPERIMENTAL | LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week. |
| Placebo | PLACEBO_COMPARATOR | Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week. |
| Valsartan 80 mg | ACTIVE_COMPARATOR | Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. |
| Valsartan 160 mg | ACTIVE_COMPARATOR | Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsatan and AHU377 (5 tablets and 2 capsules) daily. |
| Valsartan 320 mg | ACTIVE_COMPARATOR | Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily. |
| AHU377 200 mg | EXPERIMENTAL | Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily. |
| Name | Type | Description |
|---|---|---|
| LCZ696 | DRUG | - |
| Olmesartan | DRUG | - |
| Placebo of LCZ696 | DRUG | - |
| Placebo of Olmesartan | DRUG | - |
| LCZ696 matching placebo | DRUG | LCZ696 Matching Placebo tablet |
| Olmesartan matching placebo | DRUG | Olmesartan matching placebo capsule |
| amlodipine | DRUG | amlodipine 2.5 mg or 5 mg tablets |
| hydrochlorothiazide | DRUG | hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets |
| Placebo | DRUG | Matching placebo to LCZ696 and amlodipine. |
| Valsartan | DRUG | 160 mg tablets |
| AHU377 | DRUG | - |
Inclusion Criteria: * patients with mild to moderate hypertension, untreated or currently taking antihypertensive therapy * treated patients (using antihypertensive drugs within 4 weeks prior to first visit) must have an office msSBP ≥ 145 mmHg and \< 180 mmHg after washout epoch and after 4 weeks ...