- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00343395
Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study
March 15, 2011 updated by: Intermountain Health Care, Inc.
A Single-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Combined Rosiglitazone/Metformin (Avandamet®) vs. Placebo on Serological Outcomes in Non-Diabetic Patients With Stable Coronary Syndromes
Nearly half of all Americans will die from cardiovascular disease caused by the build up of atherosclerotic plaque within coronary arteries.
Most deaths in these patients arise from the development of acute coronary syndromes (ACS) such as myocardial infarction, unstable angina, or sudden death.
ACS is characterized by coronary plaque erosion or rupture, which is triggered by endothelial changes, including inflammation, and thrombosis.
Diabetes, with insulin resistance as a major component, has been shown to engender adverse metabolic events within the endothelial cell [1], including impaired endothelial function, augmented vasoconstriction, increased inflammation and thrombosis.
Activation of the transcription factors nuclear factor KB (NF-KB) and activator protein 1 (AP-1) induces inflammatory gene expression, with liberation of leukocyte-attracting chemokines, increased production of inflammatory cytokines, and augmented expression of cellular adhesion molecules.
These metabolic processes may therefore play a significant role in the development of ACS.The hypothesis is that rosiglitazone and metformin, or the combination of both may provide positive anti-atherogenic effect, even among patients without diabetes.
This pilot study proposes to evaluate the effect of placebo vs. combined rosiglitazone/metformin (Avandamet®) on surrogate blood markers of atherosclerosis activity among non-diabetic and pre-diabetic patients with known stable coronary syndromes.
This will provide further evidence justifying a large definitive outcomes-based clinical trial.
Study Overview
Detailed Description
This is a single-center, randomized, double-blind trial comparing combined rosiglitazone/metformin (Avandametä) to placebo in subjects with normal or intermediate fasting glucose (IFG) and stable coronary artery disease.Subjects meeting entry criteria will be randomized in a 1:1 ratio to receive either placebo or combined rosiglitazone/metformin (Avandametä) 4/1000 mg.
Laboratory specimens including high sensitivity C-reactive protein (hs-CRP), glucose, HgbA1C, complete lipid profile, will be obtained after a 10 hour fast as specified by study visits.
Subjects will return for repeat study visits at 2, 4, 6 and 8 months for repeat laboratory evaluations, including safety labs consisting of serum creatinine, liver enzymes, and a CBC.
Additionally, subjects will have IL-6 and TNF-a measured for research purposes at baseline and subsequent follow-up visits.
All subjects will be followed for a minimum of 8 months.
This pilot study proposes to evaluate the effect of placebo, or combined rosiglitazone/metformin onsurrogate blood markers of atherosclerosis activity among non-diabetic and pre-diabetic patients with known stable coronary syndromes.
Study Type
Interventional
Enrollment (Anticipated)
200
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Utah
-
Murray, Utah, United States, 84157
- Intermountain Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- The patient (male or non-pregnant female) must be > 18 years of age.
- The patient or legally authorized representative must sign a written informed consent, prior to the procedure, using a form that is approved by the local Institutional Review Board.
- Angiographically documented coronary artery disease defined as the presence of at least one 50% or greater stenosis of a major coronary artery.
- Stabilized post any prior ACS event (i.e., without ongoing ischemic rest pain, congestive heart failure, or malignant arrhythmias) for at least 3 months
- Fasting blood glucose 87-125 mg/dL
Exclusion Criteria:
- Age <18 years
- Known hypersensitivity to metformin or rosiglitazone
- Renal insufficiency defined as calculated creatinine clearance (CrCl) <40 mL/min using the following formula:
Men: CrCL (mL/min) = Weight (kg) x (140-age) 72 x serum creatinine (mg/dL) Women: 0.85 x the value calculated for men
- Pregnant and/or lactating women, and women of child bearing potential are excluded from this trial
- Co-morbidity such that the patient is not expected to survive >2 years
- Current therapy with rosiglitazone or metformin
- PCI within the previous six months (other than for the qualifying event)
- Prior CABG within the previous two months, scheduled CABG, or a decision to perform CABG made prior to enrollment
- Overt diabetes mellitus (FBG>126 or antidiabetic therapy)
- Any diagnosis of congestive heart failure
- Obstructive hepatobiliary disease or other significant hepatic disease (defined as the presence of at least one of the following: AST, ALT, GGT, total bilirubin, or alkaline phosphatase >3x upper limit normal, not related to MI
- Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
2/500 mg
|
Active Comparator: Avandamet
AVANDAMET 2/500 mg
|
2/500 mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein.
Time Frame: Study completion
|
Study completion
|
To demonstrate the safety of the interventions on clinical outcomes (death, MI, cardiovascular hospitalizations) and serious drug-related adverse events.
Time Frame: Study completion
|
Study completion
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To demonstrate the effect (change from baseline) of each study intervention on lipid levels
Time Frame: Study completion
|
Study completion
|
To demonstrate the effect (change from baseline) of each study intervention on inflammatory marker levels other than hs-CRP
Time Frame: Study completion
|
Study completion
|
To demonstrate the effect (change from baseline) of each study intervention on HgbA1C
Time Frame: Study completion
|
Study completion
|
To demonstrate the effect (change from baseline) of each study intervention on fasting blood glucose
Time Frame: Study completion
|
Study completion
|
Safety: Differences in adverse events between the two arms
Time Frame: Interim; completion of study
|
Interim; completion of study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2006
Primary Completion (Actual)
November 1, 2007
Study Completion (Actual)
January 1, 2008
Study Registration Dates
First Submitted
June 21, 2006
First Submitted That Met QC Criteria
June 21, 2006
First Posted (Estimate)
June 23, 2006
Study Record Updates
Last Update Posted (Estimate)
March 17, 2011
Last Update Submitted That Met QC Criteria
March 15, 2011
Last Verified
March 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 128-013
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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