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Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study

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ClinicalTrials.gov Identifier: NCT00343395
Recruitment Status : Terminated (FDA concerns regarding Avandamet)
First Posted : June 23, 2006
Last Update Posted : March 17, 2011
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Intermountain Health Care, Inc.

Tracking Information
First Submitted Date  ICMJE June 21, 2006
First Posted Date  ICMJE June 23, 2006
Last Update Posted Date March 17, 2011
Study Start Date  ICMJE June 2006
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2009)
  • To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein. [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2006)
  • To demonstrate, in nondiabetic (fasting blood glucose <126 mg/dL) subjects with stable coronary artery disease (>one major vessel with ³50% stenosis), the effect of placebo or combined rosiglitazone/metformin on the following parameters:
  • To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein.
  • To demonstrate the safety of the interventions on clinical outcomes (death, MI, cardiovascular hospitalizations) and serious drug-related adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2009)
  • To demonstrate the effect (change from baseline) of each study intervention on lipid levels [ Time Frame: 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 ]
  • To demonstrate the effect (change from baseline) of each study intervention on HgbA1C [ Time Frame: Study completion ]
  • To demonstrate the effect (change from baseline) of each study intervention on fasting blood glucose [ Time Frame: Study completion ]
  • Safety: Differences in adverse events between the two arms [ Time Frame: Interim; completion of study ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2006)
  • To demonstrate the effect (change from baseline) of each study intervention on lipid levels
  • To demonstrate the effect (change from baseline) of each study intervention on inflammatory marker levels other than hs-CRP
  • To demonstrate the effect (change from baseline) of each study intervention on HgbA1C
  • To demonstrate the effect (change from baseline) of each study intervention on fasting blood glucose
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Coronary Artery Disease
Intervention  ICMJE Drug: AVANDAMET
2/500 mg
Study Arms  ICMJE
  • Active Comparator: Avandamet
    AVANDAMET 2/500 mg
    Intervention: Drug: AVANDAMET
  • Placebo Comparator: Placebo
    Intervention: Drug: AVANDAMET
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Estimated Enrollment  ICMJE
 (submitted: June 21, 2006)
200
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2008
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00343395
Other Study ID Numbers  ICMJE 128-013
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party J. Brent Muhlestein, MD, Intermountain Healthcare
Study Sponsor  ICMJE Intermountain Health Care, Inc.
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: Joseph B Muhlestein, MD Intermountain Healthcare, LDS Hospital
PRS Account Intermountain Health Care, Inc.
Verification Date March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP