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

Novartis

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Aliskiren; Drug: hydrochlorothiazide; Drug: Amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00797862

CSPA100A2307

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,254 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,254 participants in 3 patient groups

Aliskiren + Amlodipine

Experimental group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: hydrochlorothiazide

Drug: Aliskiren

Aliskiren Start - Amlodipine Add-On

Experimental group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: hydrochlorothiazide

Drug: Aliskiren

Amlodipine Start- Aliskiren Add-On

Experimental group

Description:

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.

Treatment:

Drug: Amlodipine

Drug: hydrochlorothiazide

Drug: Aliskiren