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

NCT00343395 | Terminated Phase 4

• 1 other identifier: 128-013
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

rosiglitazone; metformin; hs-CRP; inflammation

Outcome Measures

Primary Outcomes (2)

• To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein.

  Study completion

• To demonstrate the safety of the interventions on clinical outcomes (death, MI, cardiovascular hospitalizations) and serious drug-related adverse events.

  Study completion

Secondary Outcomes (5)

• To demonstrate the effect (change from baseline) of each study intervention on lipid levels

  Study completion

• To demonstrate the effect (change from baseline) of each study intervention on inflammatory marker levels other than hs-CRP

  Study completion

• To demonstrate the effect (change from baseline) of each study intervention on HgbA1C

  Study completion

• To demonstrate the effect (change from baseline) of each study intervention on fasting blood glucose

  Study completion

• Safety: Differences in adverse events between the two arms

  Interim; completion of study

Study Arms (2)

Avandamet

ACTIVE COMPARATOR

AVANDAMET 2/500 mg

Drug: AVANDAMET

Placebo

PLACEBO COMPARATOR

Drug: AVANDAMET

Interventions

AVANDAMET DRUG

2/500 mg

Avandamet; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Intermountain Health Care, Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease; Inflammation

Interventions

rosiglitazone-metformin combination

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Joseph B Muhlestein, MD

  Intermountain Healthcare, LDS Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 21, 2006
• First Posted: June 23, 2006
• Study Start: June 1, 2006
• Primary Completion: November 1, 2007
• Study Completion: January 1, 2008
• Last Updated: March 17, 2011

Record last verified: 2011-03

Locations

US (1)