Clinical trial NCT00228176: Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant
Official title: Randomized, Multicenter, Double-blind, Placebo-controlled, Two-arm Parallel Group Trial of Rimonabant 20-mg od, for Inhibition of Atherosclerosis Progression Assessed by Carotid Artery Intima-media Thickness (CIMT), in Overweight Patients With Additional Risk Factors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carotid Artery Plaque
Arteriosclerosis
Obesity
Metabolic Syndrome X
Keywords: Metabolic syndrome
Carotid Atherosclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-28
Enrollment: 661
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objectives:

* Primary: To evaluate the effect of rimonabant 20-mg once daily in comparison with placebo, on the quantitative progression of atherosclerosis as assessed by carotid artery intima-media thickness (CIMT)
* Secondary: To evaluate the safety and tolerability of the above rimonabant regimen in the study population of atherosclerosis patients.

Detailed description: This is a Phase III, prospective, multicentre, multinational, randomized, double-blind, placebo-controlled, 2-arm parallel group trial (rimonabant 20-mg od vs placebo). There will be a three-stage screening process including successively a Screening visit, a Screening CIMT and a validation of the Screening CIMT by the Imaging Core Laboratory. Patients complying with all inclusion and exclusion criteria will be randomized in one of the 2 treatment groups less than two weeks after Screening visit. Study drug (rimonabant 20 mg od or matching placebo) will be administered during 30 to 32 months. At inclusion, patients will be counseled to follow a mild hypocaloric diet, to increase their exercise level, and to stop smoking (if smokers). Glucose/lipid parameters will be assessed at Baseline and every 6 months until the Month 30 visit. CIMT will be performed at Baseline and every 6 months until final assessment at Month 30 (primary endpoint).A post-treatment follow-up visit at Month 35 will allow the collection of all adverse events and cardiovascular outcomes occurring after last study drug administration

Eligibility criteria: Inclusion Criteria:

* Written and signed informed consent
* Age greater than or equal to 55 years
* Abdominal obesity defined by waist circumference \> 88 cm (35 inches) in women and \> 102 cm (40 inches) in men
* Metabolic syndrome diagnosed on the basis of at least two of the following additional risk factors:

  1. Triglyceride level equal to or greater than 150 mg/dL
  2. HDL cholesterol less than 40 mg/dL in men or 50 mg/dL in women
  3. Fasting glucose of equal to or greater than 110 mg/dL
  4. High blood pressure defined as equal to or greater than 140 mmHg systolic and/or equal to or greater than 90 mmHg diastolic at screening visit or current treatment by antihypertensive medication.
* Ultrasonographic evidence at Screening quantitative B-mode ultrasound imaging of a minimal CIMT measurement of greater than or equal to 0.7 mm in either of the far walls of the common carotid artery, and maximal CIMT measurement less than 3 mm in any carotid artery segment.
* All 6 carotid artery segments must have ultrasound images for all CIMT measurements
* Screening CIMT recording deemed to be of acceptable CIMT image quality, and demonstrating adherence to the CIMT interrogation protocol, as determined by the Imaging Core Laboratory's assessment.

Exclusion Criteria:

* History of very low calorie diet or surgical procedures for weight loss within 6 months prior to screening visit
* Obesity of known endocrine origin
* Uncontrolled diabetes, i.e. with HbA1c \> 10%
* Anticipated survival less than 27 months
* Presence of any severe medical or psychological condition, that in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study
* Presence of any other condition (e.g. geographic, social, or other), actual or anticipated, that the Investigator feels would restrict or limit the subject's participation for the duration of the study
* Receipt of any investigational treatment (drug or device) within 30 days prior to Screening
* Previous participation in a rimonabant study
* Total occlusion of any carotid artery segment
* Previous history of carotid intervention
* Patient considered at high risk of carotid intervention during the next 27 months

Primary outcomes:
measure: Absolute change from baseline in averaged per patient carotid artery intima-media thickness (CIMT)
timeFrame: Month 30
Secondary outcomes:
measure: First occurrence of any component of stroke/myocardial infarction (MI)/cardiovascular death
timeFrame: From randomization to Month 35
measure: First occurrence of any component of stroke/MI/cardiovascular death/hospitalization for revascularization procedure, unstable angina, transient ischemic attack (TIA)
timeFrame: From randomization to Month 35
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: John JP Kastelein, MD
role: STUDY_CHAIR
References:
citation: O'Leary DH, Reuwer AQ, Nissen SE, Despres JP, Deanfield JE, Brown MW, Zhou R, Zabbatino SM, Job B, Kastelein JJ, Visseren FL; AUDITOR investigators. Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial. Heart. 2011 Jul;97(14):1143-50. doi: 10.1136/hrt.2011.223446. Epub 2011 May 24.