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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00765674
First received: October 2, 2008
Last updated: April 15, 2011
Last verified: April 2011
  Purpose

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


Condition Intervention Phase
Hypertension
Drug: Aliskiren
Drug: Amlodipine
Drug: Hydrochlorothiazide (HCTZ)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Achieving Blood Pressure Control at the End of the Study (Week 8) [ Time Frame: End of study (Week 8) ] [ Designated as safety issue: No ]
    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.

  • Change in Mean 24-hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study (Week 8) [ Time Frame: Baseline to end of study (Week 8) ] [ Designated as safety issue: No ]
    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.


Enrollment: 1191
Study Start Date: September 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aliskiren / amlodipine
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
150 and 300 mg tablets
Drug: Amlodipine
5 and 10 mg capsules
Drug: Placebo
tablet
Drug: Placebo
capsules
Experimental: Aliskiren / hydrochlorothiazide
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
150 and 300 mg tablets
Drug: Hydrochlorothiazide (HCTZ)
12.5 and 25 mg capsules
Drug: Placebo
tablet
Drug: Placebo
capsules
Experimental: Amlodipine / hydrochlorothiazide
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
5 and 10 mg capsules
Drug: Hydrochlorothiazide (HCTZ)
12.5 and 25 mg capsules
Drug: Placebo
tablet
Experimental: Aliskiren / amlodipine / hydrochlorothiazide
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
150 and 300 mg tablets
Drug: Amlodipine
5 and 10 mg capsules
Drug: Hydrochlorothiazide (HCTZ)
12.5 and 25 mg capsules
Drug: Placebo
tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00765674

Locations
United States, Colorado
Investigative Site
Denver, Colorado, United States
Australia
Investigative Site
Sydney, Australia
Canada
Investigative Site
Ottawa, Canada
Denmark
Investigative Site
Copenhagen, Denmark
Germany
Investigative Site
Berlin, Germany
Israel
Investigative Site
Jerusalem, Israel
Italy
Investigative Site
Rome, Italy
Latvia
Investigative Site
Riga, Latvia
Lithuania
Investigative Site
Vilnius, Lithuania
Romania
Investigative Site
Bucharest, Romania
Sweden
Investigative Site
Stockholm, Sweden
Turkey
Investigative Site
Ankara, Turkey
Sponsors and Collaborators
Novartis
  More Information

No publications provided

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00765674     History of Changes
Other Study ID Numbers: CSAH100A2302
Study First Received: October 2, 2008
Results First Received: January 12, 2011
Last Updated: April 15, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada
Italy: National Institute of Health
Sweden: Medical Products Agency
Romania: National Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration
Denmark: Danish Medicines Agency
Israel: Ministry of Health
Lithuania: State Medicine Control Agency - Ministry of Health
Zanzibar: Ministry of Health and Social Welfare
Latvia: State Agency of Medicines

Keywords provided by Novartis:
aliskiren
antihypertensive
hypertension
renin inhibitor
moderate-severe hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Amlodipine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Vasodilator Agents

ClinicalTrials.gov processed this record on August 25, 2014