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

Sanofi

Status and phase: Completed; Phase 4

Conditions: Hypertension

Treatments: Drug: Hydrochlorothiazide; Drug: Valsartan/hydrochlorothiazide; Drug: Irbesartan/hydrochlorothiazide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00500604

IRBEH_R_02584

Details and patient eligibility

About

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

Enrollment: 1,617 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,617 participants in 2 patient groups

A

Experimental group

Description:

* 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.

Treatment:

Drug: Hydrochlorothiazide

Drug: Irbesartan/hydrochlorothiazide

B

Active Comparator group

Description:

* 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.

Treatment:

Drug: Hydrochlorothiazide

Drug: Valsartan/hydrochlorothiazide