Efficacy of Irbesartan/Hydrochlorothiazide Versus Valsartan/Hydrochlorothiazide in Mild to Moderate Hypertension (COSIMA2)

A Comparative Study of the Efficacy of Irbesartan/Hydrochlorothiazide 300/25 mg Versus Valsartan/Hydrochlorothiazide 160/25 mg Using Home Blood Pressure Monitoring in the Treatment of Mild to Moderate Hypertension

The primary objective is to compare the efficacy of irbesartan/hydrochlorothiazide 300/25mg against valsartan/hydrochlorothiazide 160/25mg in reducing mean systolic blood pressure (SBP) as measured by home blood pressure monitoring (HBPM) after 24 weeks compared with baseline.

The secondary objectives are:

• To compare the percentage of patients with normal blood pressure as measured by HBPM and at the doctor's office at weeks 16 and 24
• To compare the differences in mean Diastolic Blood Pressure (DBP), mean morning and evening SBP and DBP evaluated by HBPM at weeks 16 and 24
• To compare the difference in mean SBP evaluated by HBPM at week 16
• To compare the differences in mean SBP and DBP evaluated at the doctor's office at weeks 16 and 24
• To determine the incidence and severity of adverse events

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Irbesartan/hydrochlorothiazide; Drug: Hydrochlorothiazide; Drug: Valsartan/hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 1617
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Sanofi-Aventis Administrative Office
• Hong Kong
  • Hong Kong, Hong Kong
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Indonesia
  • Jakarta, Indonesia
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Malaysia
  • Kuala Lumpur, Malaysia
    • Sanofi-Aventis Administrative Office
• Morocco
  • Casablanca, Morocco
    • Sanofi-Aventis Administrative Office
• Pakistan
  • Karachi, Pakistan
    • Sanofi-Aventis Administrative Office
• Philippines
  • Makati City, Philippines
    • Sanofi-Aventis Administrative Office
• Singapore
  • Singapore, Singapore
    • Sanofi-Aventis Administrative Office
• Taiwan
  • Taipei, Taiwan
    • Sanofi-Aventis Administrative Office
• Thailand
  • Bangkok, Thailand
    • Sanofi-Aventis Administrative Office
• Tunisia
  • Megrine, Tunisia
    • Sanofi-Aventis Administrative Office
• Vietnam
  • Ho Chi Minh City, Vietnam
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Established essential hypertension, untreated or treated but uncontrolled with treatment:

  • Office SBP ≥ 160 mmHg for untreated patients
  • Office SBP ≥ 140 mmHg for patients already treated with an antihypertensive drug.

• Previous antihypertensive therapy must have been implemented for a minimum of 4 weeks and must be either monotherapy or one of the following permitted combination drugs:

  • ACE inhibitor / calcium channel blocker
  • Beta blocker / calcium channel blocker
  • Beta blocker / low dose diuretic
  • ACE inhibitor / low dose diuretic

Exclusion Criteria:

• SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg evaluated at doctor's office at Visit 1
• Known or suspected causes of secondary hypertension
• Patient with bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, a renal transplant or only has one functioning kidney
• Type 1 diabetes mellitus
• Significant cardiovascular, neurological, endocrine, renal, metabolic, or gastrointestinal disease, a malignancy or any other diseases considered by the Investigator to make participation in the study not in the best interest of the subject
• Known hypersensitivity to diuretics or sulphonamides or history of angioedema or cough related to the administration of an angiotensin II receptor antagonist or any combination of the drugs used
• Known contraindications to any of the study drugs
• Concomitant use of any other antihypertensive treatment
• Use of any of the investigational products for this study within the 3 months prior to the study
• Inability to obtain a valid HBPM recording i.e., obesity, arm circumference > 32 cm or arrhythmia
• Administration of any other investigational drug in the last 30 days before enrolment and during the course of the study
• Pregnant or breast-feeding women
• Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; period 1: Hydrochlorothiazide 12.5 mg for 3-5 weeks; period 2: One 150/12.5mg tablet every morning for 8 weeks.; period 3: One 300/12.5mg tablet every morning for 8 weeks.; period 4: Two 150/12.5mg tablets every morning for 8 weeks.	Drug: Irbesartan/hydrochlorothiazide; 150/12.5mg tablet and 300/12.5mg tablet; Drug: Hydrochlorothiazide; 12.5 mg administered orally, once daily in the morning
Active Comparator: B; period 1: Hydrochlorothiazide 12.5 mg for 3-5 weeks; period 2: One 80/12.5mg tablet every morning for 8 weeks.; period 3: One 160/12.5mg tablet every morning for 8 weeks.; period 4: Two 80/12.5mg tablets every morning for 8 weeks.	Drug: Hydrochlorothiazide; 12.5 mg administered orally, once daily in the morning; Drug: Valsartan/hydrochlorothiazide; 80/12.5mg tablet and 160/12.5mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in mean SBP as measured by HBPM	From week 0 to week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Reduction in mean DBP as measured by HBPM	From week 0 to weeks 16 and 24
Reduction in mean morning and evening SBP as measured by HBPM	From week 0 to weeks 16 and 24
Reduction in mean morning and evening DBP as measured by HBPM	From week 0 to weeks 16 and 24
Reduction in mean SBP and mean DBP evaluated at the doctor's office	From week 0 to weeks 16 and 24
Number of normalised patients as measured by HBPM	From week 0 to weeks 16 and 24
Number of normalised patients evaluated at the doctor's office	From week 0 to weeks 16 and 24
Reduction in mean SBP as measured by HBPM	From week 0 to week 16
Adverse events, vital signs, laboratory tests	From visit 1 to end of study

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Benedict Blayney, Sanofi

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: July 11, 2007
• First Submitted That Met QC Criteria: July 11, 2007
• First Posted (Estimate): July 12, 2007

Study Record Updates

• Last Update Posted (Estimate): July 19, 2010
• Last Update Submitted That Met QC Criteria: July 16, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Valsartan; Hydrochlorothiazide; Irbesartan
• Other Study ID Numbers: IRBEH_R_02584