Aliskiren Plus HCTZ Compared to Aliskiren in Metabolic Syndrome Patients With Stage 2 Systolic Hypertension

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the blood pressure lowering effect and safety of aliskiren in combination with Hydrochlorothiazide (HCTZ) compared to aliskiren monotherapy when given to metabolic syndrome patients with stage 2 systolic hypertension (mean sitting systolic blood pressure [msSBP] ≥ 160 mm Hg and < 200 mm Hg).

Official Title
-----------------
An 8-week Randomized, Double-blind, Parallel-group, Multi-center, Forced-titration Study to Evaluate the Efficacy and Safety of Aliskiren Plus HCTZ Compared to Aliskiren Monotherapy in Metabolic Syndrome Patients With Stage 2 Hypertension

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Aliskiren
* Drug: Hydrochlorothiazide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are eligible and able to participate in the study, and who give written informed consent before any assessment is performed. Male or female outpatients ≥ 18 years old. Patients with stage 2 systolic hypertension. Patients must have a msSBP ≥160 mmHg and <200 mmHg at Study Visit 5 (randomization). Patients who have stage 2 systolic hypertension that meet at least 2 additional components of the metabolic syndrome as defined by the National *Cholesterol Education program (NCEP) criteria: Abdominal obesity (waist circumference > than 102 cm for men and > 88 cm for women) Current triglycerides ≥ 150 mg/dL or medical treatment for this condition. Current HDL- Cholesterol <40 mg/dL in men and <50 mg/dL in women or medical treatment for this condition. Fasting glucose >100 mg/dL and <126 mg/dL Exclusion Criteria: Office blood pressure measured by cuff (msDBP ≥ 110 mmHg and or msSBP ≥ 200 mmHg) at any visit. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer. Use of aliskiren and/or a fixed dose combination of aliskiren HCTZ or participation in a clinical trial that had aliskiren and/or aliskiren HCTZ as treatment within 30 days of Visit 1. History of hypersensitivity to any of the medications or to drugs belonging to a similar therapeutic class (diuretics or renin inhibitors) as the study drugs. History or evidence of secondary form of hypertension. Refractory hypertension, defined as unresponsive to triple drug therapy at the maximum dose of each drug, one of which must be a diuretic, and not at blood pressure goal (140/90mmHg). Therapy with a fixed dose combination of two active substances represent two drugs. Patients on 4 or more antihypertensive medications.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren plus Hydrochlorothiazide<br>Aliskiren (150 mg) plus Hydrochlorothiazide (12.5 mg) for one week. Subsequently up-titrated to Aliskiren (300 mg) plus Hydrochlorothiazide (25 mg). Medication was taken once daily in oral form. | Drug: Aliskiren<br>* Aliskiren 150 mg or 300 mg taken once daily in oral form<br>Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide 12.5 mg or 25 mg taken once daily in oral form.<br>|
| Active Comparator: Aliskiren<br>Aliskiren (150 mg) for one week. Subsequently up-titrated to Aliskiren (300 mg). Medication was taken once daily in oral form. | Drug: Aliskiren<br>* Aliskiren 150 mg or 300 mg taken once daily in oral form<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in Mean Sitting Systolic Blood Pressure (msSBP) |  | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in Mean Sitting Diastolic Blood Pressure (msDBP) |  | 8 weeks | 
| Percentage of Participants With Blood Pressure Response at Week 8 | Response is defined as a patient with msSBP < 140 mmHg or a decrease from baseline ≥ 20 mmHg in msSBP during eight weeks of treatment. | 8 weeks | 
| Percentage of Patients Achieving Blood Pressure Control at Week 8 | Blood pressure control is defined as a patient who achieves a target Blood Pressure of mean sitting Systolic Blood Pressure / mean sitting Diastolic Blood pressure < 140/90 mmHg. | 8 weeks | 
| Change From Baseline to Week 8 in Pulse Pressure |  | Baseline and Week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypertension, Metabolic Syndrome, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, stage 2