Safety and Efficacy of Aliskiren + Hydrochlorothiazide (± Amlodipine 5 mg) in Patients With Moderate Hypertension

NCT00867490 | Completed Phase 3 Results

• 1 other identifier: CSPH100ADE01
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety and efficacy of aliskiren plus hydrochlorothiazide (HCTZ) in patients who do not achieve controlled blood pressure levels after treatment with another specified antihypertensive medication. There was an optional study extension for the first eligible 60 patients who wanted to participate that contains the triple therapy with amlodipine 5 mg and aliskiren 300 mg plus HCTZ 25 mg.

Conditions

Hypertension

Keywords

Hypertension; aliskiren; cardiovascular diseases

Outcome Measures

Primary Outcomes (2)

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study

  The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.

  Baseline Phase 2 to end of Phase 2

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study

  The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.

  Baseline Phase 3 to end of Phase 3

Secondary Outcomes (10)

• Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study

  Baseline Phase 2 to end of Phase 2

• Change in Sitting Pulse Pressure During the Core Phase of the Study

  Baseline Phase 2 to end of Phase 2

• Change in Sitting Pulse Rate During the Core Phase of the Study

  Baseline Phase 2 to end of Phase 2

• Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study

  Baseline Phase 2 to end of Phase 2

• Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study

  Baseline Phase 2 to end of Phase 2

Study Arms (1)

Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine

EXPERIMENTAL

Drug: Candesartan+HCTZ - Phase 1; Drug: Aliskiren+HCTZ - Phase 2; Drug: Aliskiren+HCTZ+amlodipine - Phase 3

Interventions

Candesartan+HCTZ - Phase 1 DRUG

4 weeks treatment with candesartan 32 mg (two 16 mg tablets) plus hydrochlorothiazide 25 mg (two 12.5 mg tablets) taken orally with water in the morning between 7 and 10 am.

Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine

Aliskiren+HCTZ - Phase 2 DRUG

Patients with uncontrolled mean sitting diastolic blood pressure (msDBP ≥ 90 mm Hg) at the end of Phase 1 were treated for 4 weeks with aliskiren 300 mg plus hydrochlorothiazide 25 mg in a single tablet taken orally with water in the morning between 7 and 10 am.

Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine

Aliskiren+HCTZ+amlodipine - Phase 3 DRUG

The first 60 patients with uncontrolled mean sitting systolic or diastolic blood pressure (msDBP ≥ 90 mm Hg and/or msSBP ≥ 140 mm Hg) at the end of Phase 2 were offered 4 weeks treatment with aliskiren 300 mg plus HCTZ 25 mg in a single tablet plus an amlodipine 5 mg tablet taken orally with water in the morning between 7 and 10 am.

Candesartan+HCTZ, aliskiren+HCTZ, aliskiren+HCTZ+amlodipine

Eligibility Criteria

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

You may qualify if:

• \- Patients with mean sitting diastolic blood pressure ≥ 100 mmHg and \< 110 mmHg
• \- msSBP ≥ 140 mm Hg and/or msDBP ≥ 90 mm Hg at Visit 5 of the core study

You may not qualify if:

• Patients with mean diastolic blood pressure ≥ 110 mmHg or mean systolic blood pressure ≥ 180 mmHg
• Patients with prior stroke, hypertensive encephalopathy or heart attack
• Patients with type 1 diabetes mellitus
• Patients with type 2 diabetes mellitus with poor glucose control
• Premature discontinuation in the core study or failure to comply with the core study protocol
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures, known or suspected contraindications to diuretics as described in the SmPC (particularly amlodipine 5 mg), e.g. severe hypotension, shock - including cardiogenic shock, obstructions impairing the flow out of the left ventricle (e.g. significant aortic stenosis)
• Any patient that the investigator decides should not participate in the extension study for medical reasons

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Investigative Site

Chemnitz, Germany

Location

Related Publications (1)

• Schweizer J, Ulmer HJ, Benduhn H, Klebs S. Efficacy and tolerability of aliskiren 300 mg/hydrochlorothiazide 25 mg (+/- amlodipine 5 mg) in hypertensive patients not controlled by candesartan 32 mg plus HCT 25 mg. Curr Med Res Opin. 2011 Jan;27(1):131-40. doi: 10.1185/03007995.2010.537318. Epub 2010 Nov 30.

  PMID: 21117946 DERIVED

MeSH Terms

Conditions

Hypertension; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases

Limitations and Caveats

The Phases of this study were entered in separate tables for outcomes and the Phases for SAEs and the AEs were entered all in one table.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 20, 2009
• First Posted: March 23, 2009
• Study Start: March 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: May 6, 2011
• Results First Posted: February 1, 2011

Record last verified: 2011-05

Locations

DE (1)