Aliskiren and the Calcium Channel Blocker Amlodipine Combination as an Initial Treatment Strategy for Hypertension

Study Overview
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Brief Summary
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This study will compare the safety and efficacy of initial combination treatment with aliskiren + amlodipine to sequential add-on treatment strategies with aliskiren or amlodipine in patients with hypertension.

Detailed Description
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This study was designed to evaluate if patients with hypertension treated early with a combination therapy would achieve better blood pressure (BP) control, than patients being treated with a classical sequential add-on therapy. The study compared the effects of the two treatment strategies: Treatment initiation on a single compound, either with aliskiren or amlodipine, and then continuation with the combination of both versus treatment initiation with the combination of aliskiren/amlodipine and then continuation with the combination. The study also evaluated if the overall mean sitting systolic blood pressure (msSBP)-lowering effect during the study, as well as the change from baseline to study end in msSBP, are superior in the group having received combination therapy from the beginning. The study further evaluated the BP-lowering efficacy and tolerability of both treatment strategies.

Official Title
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A Randomized, 32 Week Double-blind, Parallel-group, Multicenter Study to Compare the Efficacy and Safety of Initiating Treatment With Combination (Aliskiren/Amlodipine) Therapy in Comparison With the Sequential add-on Treatment Strategies in Patients With Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Amlodipine
* Drug: hydrochlorothiazide
* Drug: Aliskiren


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients ≥ 18 years of age Participants with essential hypertension: Naive participants must have a mean sitting Systolic Blood Pressure (msSBP) ≥ 150 mmHg and < 180 mmHg at Visit 1 and Visit 2. (Participants are considered 'naïve' if they have never been treated with any antihypertensive medication.) All participants must have a msSBP ≥ 150 mmHg and < 180 mmHg at Visit 2 Written informed consent to participate in this study prior to any study procedures Exclusion Criteria: Severe hypertension Pregnant or nursing (lactating) women Pre-menopausal women not taking accepted form of birth control Serum potassium ≥ 5.5 mEq/L (mmol/L) at Visit 1 History of cardiovascular conditions Uncontrolled Type 1 or Type 2 diabetes mellitus Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with similar chemical structures 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren + Amlodipine<br>Eligible participants received oral aliskiren 150 mg + amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of the combination treatment increased to aliskiren 300 mg + amlodipine 10 mg daily. From week 16-24, participants in this group continued combination treatment (aliskiren 300 mg + amlodipine 10 mg) for 8 weeks. At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks. | Drug: Amlodipine<br>* Amlodipine (5 mg and 10 mg) was provided as capsules taken orally once daily.<br>* Other names: Norvasc;Drug: hydrochlorothiazide<br>* Hydrochlorothiazide 12.5 mg capsules were taken orally once daily<br>* Other names: Hydro-Par;Drug: Aliskiren<br>* Aliskiren 150 mg and aliskiren 300 mg were provided as film-coated tablets, taken orally once daily.<br>* Other names: SPA 100;|
| Experimental: Aliskiren Start - Amlodipine Add-On<br>Eligible participants received oral aliskiren 150 mg daily from week 1-8. From week 8 - 16, the dose of aliskiren increased to 300 mg daily. From week 16-24, amlodipine 10 mg was added to the aliskiren 300 mg for 8 weeks (aliskiren 300 mg + amlodipine 10 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (aliskiren 300 mg + amlodipine 10 mg) for an additional 8 weeks. Total treatment period =32 weeks. | Drug: Amlodipine<br>* Amlodipine (5 mg and 10 mg) was provided as capsules taken orally once daily.<br>* Other names: Norvasc;Drug: hydrochlorothiazide<br>* Hydrochlorothiazide 12.5 mg capsules were taken orally once daily<br>* Other names: Hydro-Par;Drug: Aliskiren<br>* Aliskiren 150 mg and aliskiren 300 mg were provided as film-coated tablets, taken orally once daily.<br>* Other names: SPA 100;|
| Experimental: Amlodipine Start- Aliskiren Add-On<br>Eligible participants received oral amlodipine 5 mg daily from week 1-8. From week 8 - 16, the dose of amlodipine increased to 10 mg daily. From week 16-24, aliskiren 300 mg was added to the amlodipine 10 mg for 8 weeks (amlodipine 10 mg + aliskiren 300 mg). At week 24, if blood pressure was not adequately controlled (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg) hydrochlorothiazide 12.5 mg was added to the combination (amlodipine 10 mg + aliskiren 300 mg) for an additional 8 weeks. Total treatment period =32 weeks. | Drug: Amlodipine<br>* Amlodipine (5 mg and 10 mg) was provided as capsules taken orally once daily.<br>* Other names: Norvasc;Drug: hydrochlorothiazide<br>* Hydrochlorothiazide 12.5 mg capsules were taken orally once daily<br>* Other names: Hydro-Par;Drug: Aliskiren<br>* Aliskiren 150 mg and aliskiren 300 mg were provided as film-coated tablets, taken orally once daily.<br>* Other names: SPA 100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Mean Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) Over 8, 16 and 24 Weeks | Systolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msSBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures Analysis of Covariance (ANCOVA) model with treatment, visit, and region as factors, treatment by visit interaction and baseline msSBP as a covariate. | Baseline, 8 weeks, 16 weeks, and 24 weeks | 
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 24 | Systolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region as factors, treatment by visit interaction and baseline msSBP as a covariate. | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 32 | Diastolic Blood Pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 32 weeks of study treatment. Change at Week 32 used a separate repeated measures ANCOVA model containing Week 8, 16, 24 and 32 data. Treatment, visit and region were factors in the model, treatment by visit interaction and baseline msDBP a covariate. | Baseline to 32 weeks | 
| Overall Mean Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) Over 8, 16, and 24 Weeks | Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and over 8, 16 and 24 weeks of study treatment. The overall mean change in msDBP from baseline was estimated over three time points: Week 8, Week 16, and Week 24. Analysis used a repeated measures ANCOVA model with treatment, visit and regions as factors, treatment by visit interaction and baseline msDBP as a covariate. | Baseline, 8 weeks, 16 weeks and 24 weeks | 
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 24 | Diastolic Blood pressure was measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and 24 weeks of study treatment. Analysis used a repeated measures ANCOVA model with treatment, visit and region, as factors, treatment by visit interaction and baseline msDBP as a covariate. | Baseline to 24 weeks | 
| Percentage of Participants Achieving Overall Blood Pressure Control at 8, 16, 24 and 32 Weeks Endpoints | Systolic & Diastolic Blood Pressure were measured in a sitting position using a validated automated blood pressure monitor (the Omron device) according to Guidelines of the British Hypertension Society, at Baseline and after 8, 16 , 24 and 32 weeks. Outcome is reported as percentage of participants achieving overall blood pressure control (msSBP <140 mmHg and msDBP <90 mmHg) at weeks 8, 16, 24 & 32 endpoints. | Baseline to week 8, 16, 24 and 32 endpoints | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aliskiren, Amlodipine, Hypertension, SPA1000, Norvasc