Efficacy and Safety of Aliskiren/Amlodipine/Hydrochlorothiazide in Patients With Moderate-severe Hypertension

Study Overview
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Brief Summary
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This study evaluated the efficacy (blood pressure lowering effect) and safety of aliskiren/amlodipine/hydrochlorothiazide in patients with moderate to severe hypertension.

Official Title
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An 8 Week, Double-blind, Randomized, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren/Amlodipine/Hydrochlorothiazide in Patients With Moderate to Severe Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Amlodipine
* Drug: Hydrochlorothiazide (HCTZ)
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older msDBP and msSBP requirements: 3A: Diagnosis of moderate to severe hypertension (msSBP ≥ 160 mmHg and < 200 mmHg, and/or msDBP ≥ 100 mmHg and < 120 mmHg) at Visits 4, 5 or 6 (Qualifying BP visit) In addition, at the visit immediately prior to the above qualifying visit, patients were also to have msSBP ≥ 145 mmHg and < 200 mmHg and msDBP ≥ 95 mmHg and < 120 mmHg) at Visits 3, 5 or 5. Patients had to meet the above two sets of requirements at subsequent adjacent visits, i.e. either Visits 3 and 4, Visits 4 and 5, or Visits 5 and 6. OR 3B: msSBP ≥ 180 mmHg and < 200 mmHg with msDBP ≥ 95 mmHg and < 120 mmHg, or msDBP ≥ 110 mmHg and < 120 mmHg with msSBP ≥ 150 mmHg and < 200 mmHg after at least one week of treatment with placebo (Visit 3 and on). Exclusion Criteria: Continued use of anti-hypertensive medicines or use of 4 or more hypertensive medicines at study start Patients with an msSBP ≥ 200 mmHg or msDBP ≥ 120 mmHg at any time during the placebo run-in period were to be discontinued from the study. Extremely elevated (defined) blood pressure at any point during the study Pregnant or lactating women Pre-menopausal women not taking accepted form of birth control History or evidence of secondary form of hypertension History of cardiovascular conditions Other protocol-defined inclusion/exclusion criteria applied to the study.

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 / amlodipine<br>Patients received an aliskiren 150 mg tablet plus an amlodipine 5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus amlodipine 10 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet and a placebo capsule. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. | Drug: Aliskiren<br>* 150 and 300 mg tablets<br>Drug: Amlodipine<br>* 5 and 10 mg capsules<br>Drug: Placebo<br>* tablet<br>Drug: Placebo<br>* capsules<br>|
| Experimental: Aliskiren / hydrochlorothiazide<br>Patients received an aliskiren 150 mg tablet plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo capsule and a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. | Drug: Aliskiren<br>* 150 and 300 mg tablets<br>Drug: Hydrochlorothiazide (HCTZ)<br>* 12.5 and 25 mg capsules<br>Drug: Placebo<br>* tablet<br>Drug: Placebo<br>* capsules<br>|
| Experimental: Amlodipine / hydrochlorothiazide<br>Patients received an amlodipine 5 mg capsule plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to amlodipine 10 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received 2 placebo tablets. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. | Drug: Amlodipine<br>* 5 and 10 mg capsules<br>Drug: Hydrochlorothiazide (HCTZ)<br>* 12.5 and 25 mg capsules<br>Drug: Placebo<br>* tablet<br>|
| Experimental: Aliskiren / amlodipine / hydrochlorothiazide<br>Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed. | Drug: Aliskiren<br>* 150 and 300 mg tablets<br>Drug: Amlodipine<br>* 5 and 10 mg capsules<br>Drug: Hydrochlorothiazide (HCTZ)<br>* 12.5 and 25 mg capsules<br>Drug: Placebo<br>* tablet<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 8) | Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0.5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP. | Baseline to end of study (Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was < 0.5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP. | Baseline to end of study (Week 8) | 
| Percentage of Patients Achieving Blood Pressure Control at the End of the Study (Week 8) | Blood pressure control was defined as a msSBP/msDBP < 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. | End of study (Week 8) | 
| Change in Mean 24-hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study (Week 8) | Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed in a subset of patients twice during the study, once at baseline and again at Week 8. The ABPM device was placed on the non-dominant arm between 7:00 and 10:00 am and verification readings obtained. If they were successful, the investigator initiated the 24 hour reading and instructed the patient regarding ABPM procedures. On the next day, the ABPM device was removed if it had been worn for a minimum of 24 hours. The ABPM data were downloaded and evaluated on site. | Baseline to end of study (Week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aliskiren, antihypertensive, hypertension, renin inhibitor, moderate-severe hypertension