Clinical trial NCT00956644: Irbesartan/Amlodipine in Hypertensive Patients Uncontrolled on Amlodipine 5 mg Monotherapy
Official title: Efficacy and Safety of Irbesartan/Amlodipine Fixed Combination Therapy Compared With Amlodipine Monotherapy in Hypertensive Patients Uncontrolled on Amlodipine 5 mg Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-08-11
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Mean home systolic blood pressure
timeFrame: At randomisation and week 5
Secondary outcomes:
measure: Mean office blood pressure
timeFrame: At randomisation, week 5 and week 10
measure: Mean home diastolic blood pressure
timeFrame: At randomisation, week 5 and week 10
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 07602
city: Rio de Janeiro
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076-005
city: Rio de Janeiro
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 07605
city: São José
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 07604
city: São Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 07601
city: São Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076-004
city: São Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 076-002
city: São Paulo
country: Brazil
facility: Sanofi-Aventis Investigational Site Number 07603
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 15202
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 15203
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 15204
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 15205
city: Santiago
country: Chile
facility: Sanofi-Aventis Investigational Site Number 15206
city: Barranquilla
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 17003
city: Barranquilla
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 17004
city: Medellin
country: Colombia
facility: Sanofi-Aventis Investigational Site Number 17002
city: Alexandria
country: Egypt
facility: Sanofi-Aventis Investigational Site Number 81803
city: Alexandria
country: Egypt
facility: Sanofi-Aventis Investigational Site Number 81804
city: Cairo
country: Egypt
facility: Sanofi-Aventis Investigational Site Number 81801
city: Cairo
country: Egypt
facility: Sanofi-Aventis Investigational Site Number 81802
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Investigational Site Number 42202
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Investigational Site Number 42203
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Investigational Site Number 42204
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Investigational Site Number 42205
city: Beirut
country: Lebanon
facility: Sanofi-Aventis Investigational Site Number 42206
city: Durango
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48401
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48402
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48403
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48406
city: Guadalajara
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48404
city: Mexico
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48405
city: Mexico
country: Mexico
facility: Sanofi-Aventis Investigational Site Number 48407
city: Casablanca
country: Morocco
facility: Sanofi-Aventis Investigational Site Number 50401
city: Marrakech
country: Morocco
facility: Sanofi-Aventis Investigational Site Number 50402
city: Marrakech
country: Morocco
facility: Sanofi-Aventis Investigational Site Number 50403
city: Ariana
country: Tunisia
facility: Sanofi-Aventis Investigational Site Number 78804
city: Monastir
country: Tunisia
facility: Sanofi-Aventis Investigational Site Number 78803
city: Sfax
country: Tunisia
facility: Sanofi-Aventis Investigational Site Number 78802
city: Tunis
country: Tunisia
facility: Sanofi-Aventis Investigational Site Number 78801
city: Caracas
country: Venezuela
facility: Sanofi-Aventis Investigational Site Number 86201
Study officials:
affiliation: Sanofi
name: Nathalie Genes, MD
role: STUDY_DIRECTOR
References:
citation: Bobrie G; I-COMBINE Study Investigators. I-COMBINE study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study. Clin Ther. 2012 Aug;34(8):1705-19. doi: 10.1016/j.clinthera.2012.06.026. Epub 2012 Jul 30.