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

NCT00765674 | Completed Phase 3 Results

• 1 other identifier: CSAH100A2302
• Study Type: interventional
• Target: 1,191
• Locations: 12 countries
• Sites: 12

Brief Summary

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

Conditions

Hypertension

Keywords

aliskiren; antihypertensive; hypertension; renin inhibitor; moderate-severe hypertension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)

  Baseline to end of study (Week 8)

• Percentage of Patients Achieving Blood Pressure Control at the End of the Study (Week 8)

  End of study (Week 8)

• Change in Mean 24-hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study (Week 8)

  Baseline to end of study (Week 8)

Study Arms (4)

Aliskiren / amlodipine

EXPERIMENTAL

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; Drug: Amlodipine; Drug: Placebo

Aliskiren / hydrochlorothiazide

EXPERIMENTAL

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; Drug: Hydrochlorothiazide (HCTZ); Drug: Placebo

Amlodipine / hydrochlorothiazide

EXPERIMENTAL

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; Drug: Hydrochlorothiazide (HCTZ); Drug: Placebo

Aliskiren / amlodipine / hydrochlorothiazide

EXPERIMENTAL

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

Interventions

Aliskiren DRUG

150 and 300 mg tablets

Aliskiren / amlodipine; Aliskiren / amlodipine / hydrochlorothiazide; Aliskiren / hydrochlorothiazide

Amlodipine DRUG

5 and 10 mg capsules

Aliskiren / amlodipine; Aliskiren / amlodipine / hydrochlorothiazide; Amlodipine / hydrochlorothiazide

Hydrochlorothiazide (HCTZ) DRUG

12.5 and 25 mg capsules

Aliskiren / amlodipine / hydrochlorothiazide; Aliskiren / hydrochlorothiazide; Amlodipine / hydrochlorothiazide

Placebo DRUG

tablet

Aliskiren / amlodipine; Aliskiren / amlodipine / hydrochlorothiazide; Aliskiren / hydrochlorothiazide; Amlodipine / hydrochlorothiazide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• years of age or older
• msDBP and msSBP requirements:
• 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.
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (12)

Investigative Site

Denver, Colorado, United States

Location

Investigative Site

Sydney, Australia

Location

Investigative Site

Ottawa, Canada

Location

Investigative Site

Copenhagen, Denmark

Location

Investigative Site

Berlin, Germany

Location

Investigative Site

Jerusalem, Israel

Location

Investigative Site

Rome, Italy

Location

Investigative Site

Riga, Latvia

Location

Investigative Site

Vilnius, Lithuania

Location

Investigative Site

Bucharest, Romania

Location

Investigative Site

Stockholm, Sweden

Location

Investigative Site

Ankara, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Hypertension

Interventions

aliskiren; Amlodipine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 2, 2008
• First Posted: October 3, 2008
• Study Start: September 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: May 9, 2011
• Results First Posted: May 9, 2011

Record last verified: 2011-04

Locations

DE (1); LI (1); RO (1); US (1); DK (1); TU (1); SE (1); IT (1); IL (1); AU (1); LA (1); CA (1)