Efficacy and Safety of the Combination Aliskiren (300 mg) and Hydrochlorothiazide (25mg) to Aliskiren (300mg) Monotherapy in Patients With Staged II Hypertension

Study Overview
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Brief Summary
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This study will compare the efficacy and safety of once daily dosing of aliskiren monotherapy to once daily dosing of aliskiren and hydrochlorothiazide combination therapy in patients with Stage II hypertension over a period of 12 weeks.

Official Title
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A 12 Week, Double-blind, Randomized, Parallel Group, Multi-center Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren 300 mg and Hydrochlorothiazide 25 mg Compared to Aliskiren 300 mg in Patients With Stage II Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren/hydrochlorothiazide (HCTZ) (300/25 mg)
* Drug: Aliskiren (300 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients ≥18 years of age. Patients with a diagnosis of Stage II hypertension, defined as mean sitting Systolic Blood Pressure (msSBP) ≥ 160 mmHg and < 180 mmHg at Visit 2. Exclusion Criteria: Severe hypertension defined as msSBP ≥ 180 mmHg and/or mean sitting Diastolic Blood Pressure (msDBP) ≥ 110 mmHg. Secondary form of hypertension. Current diagnosis of heart failure (New York Heart Association [NYHA] Class II-IV). Current angina pectoris requiring pharmacological therapy (other than stable doses of oral or topical nitrates). Second or third degree heart block without a pacemaker. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, atrial fibrillation or atrial flutter, during the 12 months prior to Visit 1. Clinically significant valvular heart disease. Previous history of hypertensive encephalopathy or stroke, Transcient Ischemic Attack (TIA), heart attack, coronary bypass surgery or any PCI. Known Keith-Wagener grade III or IV hypertensive retinopathy. In the month prior to Visit 1, patients on combination antihypertensive therapy that includes more than 2 classes of antihypertensive medications. Patients on combined antihypertensive medication that contain two classes of antihypertensive medications are considered to take two antihypertensive medications. Inability to discontinue prior antihypertensive or other CV medications as required by the protocol. Patients with Type 1 diabetes mellitus. Patients with Type 2 diabetes mellitus not well controlled . Elevated Serum potassium (over 5.3 mEq/L (mmol/L). Any surgical or medical condition or the use of any medication which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs. 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren/hydrochlorothiazide (HCTZ) (300/25 mg)<br> | Drug: Aliskiren/hydrochlorothiazide (HCTZ) (300/25 mg)<br>* During the titration period, patients received aliskiren/hydrochlorothiazide (HCTZ) 150/12.5 mg for 1 week.<br>|
| Active Comparator: Aliskiren (300 mg)<br> | Drug: Aliskiren (300 mg)<br>* During the titration period, patients received aliskiren 150 mg for one week. Subsequently, patients were up-titrated and received aliskiren 300 mg.<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 (msSBP) From Baseline to End of Study (Week 12) | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. | Baseline to end of study (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 8 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. | Baseline to Week 8 | 
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 8 and to Week 12 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. | Baseline to Week 12 | 
| Percentage of Patients Achieving the Target Blood Pressure (msSBP < 140 mm Hg and msDBP < 90 mm Hg, and msSBP < 130 mm Hg and msDBP < 80 mm Hg for Diabetics) at Week 8 and Week 12 | At the first visit, blood pressure (BP) was measured in both arms and the arm having the higher BP reading was the arm used for all subsequent readings throughout the study. Patients were required to sit for five minutes with feet flat on the floor, with arm resting so that the bottom of the cuff was at the same level as the heart. BP was measured three times at 1 to 2-minute intervals at each visit using the correct cuff size. The mean BP was calculated from the 3 readings. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential Hypertension, Stage II