AUDITOR: Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant

Sponsor

Sanofi (Industry)

Overall Status

Terminated

CT.gov ID

NCT00228176

Collaborator

(none)

661

Enrollment

Locations

Arms

Duration (Months)

110.2

Patients Per Site

2.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Plaque Arteriosclerosis Obesity Metabolic Syndrome X	Drug: Rimonabant Drug: Placebo (for Rimonabant)	Phase 3

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

Study Design

Study Type:

Interventional

Actual Enrollment :

661 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2005

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rimonabant Rimonabant 20 mg once daily	Drug: Rimonabant Tablet, oral administration Other Names: SR141716 Acomplia
Placebo Comparator: Placebo Placebo (for Rimonabant) once daily.	Drug: Placebo (for Rimonabant) Tablet, oral administration

Arm

Intervention/Treatment

Experimental: Rimonabant

Rimonabant 20 mg once daily

Drug: Rimonabant

Tablet, oral administration

Other Names:

SR141716

Acomplia

Placebo Comparator: Placebo

Placebo (for Rimonabant) once daily.

Drug: Placebo (for Rimonabant)

Tablet, oral administration

Outcome Measures

Primary Outcome Measures

Absolute change from baseline in averaged per patient carotid artery intima-media thickness (CIMT) [Month 30]

Secondary Outcome Measures

First occurrence of any component of stroke/myocardial infarction (MI)/cardiovascular death [From randomization to Month 35]
First occurrence of any component of stroke/MI/cardiovascular death/hospitalization for revascularization procedure, unstable angina, transient ischemic attack (TIA) [From randomization to Month 35]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Triglyceride level equal to or greater than 150 mg/dL
HDL cholesterol less than 40 mg/dL in men or 50 mg/dL in women
Fasting glucose of equal to or greater than 110 mg/dL
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis Administrative Office	Laval		Canada
3	Sanofi-Aventis Administrative Office	Paris		France
4	Sanofi-Aventis Administrative Office	Gouda		Netherlands
5	Sanofi-Aventis Administrative Office	Barcelona		Spain
6	Sanofi-Aventis Administrative Office	Guildford Surrey		United Kingdom