Irbesartan/Amlodipine in Hypertensive Patients Uncontrolled on Amlodipine 5 mg Monotherapy (I-COMBINE)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: amlodipine; Drug: irbesartan/amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00956644

IRBAM_R_04220

Details and patient eligibility

About

Primary Objective:

• To demonstrate that the antihypertensive efficacy of the fixed combination irbesartan/amlodipine 150/5 mg is superior to that of amlodipine 5 mg monotherapy in lowering systolic blood pressure (SBP) as measured by home blood pressure measurement (HBPM) after 5 weeks of treatment (W5)

Secondary Objective:

• To compare the antihypertensive efficacy of the fixed combination irbesartan/amlodipine 150/5 mg with that of amlodipine 5 mg monotherapy after 5 weeks of treatment (W5)
• To compare the antihypertensive efficacy of the fixed combination therapy irbesartan/amlodipine 150/10 mg with that of amlodipine 10 mg monotherapy at the end of treatment (W10)
• To examine in each treatment group the change from week 5 to week 10 in SBP and diastolic blood pressure (DBP) assessed by HBPM and by office blood pressure measurement (OBPM)
• To determine the incidence and severity of adverse events

Enrollment: 406 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Established essential hypertension
• Treated with amlodipine 5 mg monotherapy for at least 4 weeks
• With uncontrolled BP defined as mean SBP = or > 145 mmHg assessed by OBPM
• Signed written inform consent obtained prior to inclusion in the study

Randomisation Criteria:

• Mean SBP = or > 135 mmHg assessed by HBPM
• Good compliance with the HBPM protocol defined as at least 12 correct measurements performed over the last 6 days of the first period of measurements
• Creatinine clearance = or > 30 ml/min, determined by Cockroft formula

Exclusion criteria

• Mean SBP = or > 180 mm Hg and/or mean DBP = or > 110 mm Hg measured at doctor's office at Visit 1
• Known or suspected causes of secondary hypertension
• Patients with bilateral artery stenosis, renal artery stenosis in a solitary kidney, renal transplant or only one functioning kidney
• Know contraindications or hypersensitivity to either amlodipine or irbesartan or to the combination or history of angioedema related to the administration of an angiotensin II receptor antagonist or any combination of the drugs used
• Known type 1 diabetes
• Know severe hepatic impairment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal or history or hepatic encephalopathy, esophageal varices, or portocaval shunt
• Known severe renal impairment (creatinine clearance < 30 ml/mn)
• Concomitant use of any other antihypertensive treatment
• Administration of any other investigational drug within 30 days before inclusion
• Inability to obtain a valid automatic BP measurement recording
• Presence of any severe medical or psychological condition that, in the opinion of the investigator, indicate that participation in the study is not in the best interest of the patient
• Presence of any other conditions (e.g.: geographical, social, etc) that would restrict or limit the patient participation for the duration of the study
• Pregnant or breast feeding women
• Women of childbearing potential unable or unwilling to use an acceptable method to avoid pregnancy for the entire study period

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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406 participants in 2 patient groups

irbesartan/amlodipine

Experimental group

Description:

Before randomisation : amlodipine 5 mg for 7 to 10 days (common to 2 arms) then After randomisation : irbesartan/amlodipine 150/5 mg fixed combination for 5 weeks followed by irbesartan/amlodipine 150/10 mg fixed combination for 5 additional weeks

Treatment:

Drug: irbesartan/amlodipine

amlodipine

Active Comparator group

Description:

Before randomisation : amlodipine 5 mg for 7 to 10 days (common to 2 arms) then After randomisation : amlodipine 5 mg for 5 weeks followed by amlodipine 10 mg for 5 additional weeks

Treatment:

Drug: amlodipine