Valsartan/Amlodipine As Compared to Losartan Treatment in Stage 2 Systolic Hypertension

Study Overview
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Brief Summary
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This study will compare the antihypertensive efficacy and safety of a valsartan/amlodipine-based treatment with a losartan-based treatment in patients with Stage 2 systolic hypertension (high blood pressure, mean systolic blood pressure greater than 160 and less than 200 mmHg).

Official Title
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A 12-week Multicenter, Randomized, Double-blind, Parallel-group, Active-control Study to Evaluate the Antihypertensive Efficacy and Safety of Valsartan/Amlodipine-based Regimen Versus a Losartan-based Regimen in Patients With Stage 2 Systolic Hypertension

Conditions
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Stage 2 Systolic Hypertension

Intervention / Treatment
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* Drug: valsartan, amlodipine, HCTZ
* Drug: Losartan, HCTZ followed by valsartan, amlodipine, HCTZ


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatient of 18 years of age or greater Stage 2 systolic hypertension defined as office Mean Sitting Systolic blood pressure (MSSBP) greater than or equal to 160 and < 200 mmHg at randomization Patients who were able to participate in the study, and who gave written informed consent before any study assessment was performed. Exclusion Criteria: Office systolic blood pressure >200 and/or mean sitting diastolic blood pressure (MSDBP) greater than or equal to 110 mmHg at Visit 1. Use of four (4) or more antihypertensive medications within 30 days of Visit 1. Refractory hypertension, defined as blood pressure >140/90 mmHg while taking three (3) drugs at the maximum dose of each drug, one of which must be a diuretic. (Therapy with a fixed-dose combination of two active medications represents two drugs). Inability to safely discontinue all antihypertensive medications for 1-2 weeks prior to randomization. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan/amlodipine/HCTZ<br>Valsartan/amlodipine-based regimen: at randomization (Visit 3) patients were treated with valsartan/amlodipine 160/5 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks, and a second forced titration at Visit 5 (Week 6) to valsartan/amlodipine/HCTZ 320/10/25 mg for the remaining 6 weeks of the study. | Drug: valsartan, amlodipine, HCTZ<br>* combination Valsartan/amlodipine160/5 mg tablet for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (6 weeks) of the study<br>|
| Active Comparator: Losartan/HCTZ<br>Losartan-based regimen: at randomization (Visit 3) patients were treated with losartan 100 mg for 3 weeks, followed by a forced titration at Visit 4 (Week 3) to losartan/HCTZ 100/25 mg. At Visit 5 (Week 6) patients were switched to valsartan/amlodipine/HCTZ 160/5/25 mg for 3 weeks and, at Visit 6 (Week 9), patients were force titrated to valsartan/amlodipine/HCTZ 320/10/25 mg for the final 3 weeks of the study. | Drug: Losartan, HCTZ followed by valsartan, amlodipine, HCTZ<br>* losartan 100mg capsule for 3 weeks; losartan 100mg capsule +HCTZ 25 mg capsule for 3 weeks; Valsartan/amlodipine 160/5mg tablet +HCTZ 25 mg capsule for 3 weeks; valsartan/amlodipine 320/10 mg tablet + HCTZ 25mg capsule for remainder (3 weeks) of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Systolic Blood Pressure After 6 Weeks | To compare the change from baseline in mean sitting systolic blood pressure (MSSBP) after 6 weeks of valsartan/amlodipine-based regimen with a losartan-based regimen in patients with Stage 2 systolic hypertension. | Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Diastolic Blood Pressure After 6 Weeks | To compare the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. | Baseline to Week 6 | 
| Cumulative Percentage of Patients Achieving Blood Pressure Control | To compare the percentage of patients achieving blood pressure control (defined as patients achieving MSSBP < 140 mmHg and MSDBP < 90 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. | 3 and 6 weeks | 
| Cumulative Percentage of Treatment Responders | To compare the percentage of treatment responders (defined as patients with MSSBP < 140 mmHg or demonstrating a decrease from baseline of ≥ 20 mmHg) after 3 and 6 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. | 3 and 6 weeks | 
| Change in Mean Sitting Systolic and Diastolic Blood Pressure After 12 Weeks | To compare the change from baseline in MSSBP and MSDBP after 12 weeks of valsartan/amlodipine-based regimen with losartan-based regimen in patients with Stage 2 systolic hypertension. | Baseline to week 12 | 
| Cumulative Percentage of Patients With Incidence of Peripheral Edema Before or at the Corresponding Visit | To assess the incidence of peripheral edema occurring with valsartan/amlodipine-based regimen versus losartan-based regimen in patients with Stage 2 systolic hypertension. | 3, 6, 9 and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, combination therapy, valsartan, cardiovascular diseases