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

Novartis

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Amlodipine; Drug: Aliskiren; Drug: Hydrochlorothiazide (HCTZ); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00765674

CSAH100A2302

Details and patient eligibility

About

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

Enrollment: 1,191 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,191 participants in 4 patient groups

Aliskiren / amlodipine

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Amlodipine

Drug: Aliskiren

Drug: Placebo

Aliskiren / hydrochlorothiazide

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Hydrochlorothiazide (HCTZ)

Drug: Aliskiren

Drug: Placebo

Amlodipine / hydrochlorothiazide

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Hydrochlorothiazide (HCTZ)

Drug: Amlodipine

Drug: Placebo

Aliskiren / amlodipine / hydrochlorothiazide

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Hydrochlorothiazide (HCTZ)

Drug: Amlodipine

Drug: Aliskiren

Drug: Placebo