Coronary Artery DiseasePhase 4NCT00343395
Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study
A Phase 4 study testing AVANDAMET in people with Coronary Artery Disease, run by Intermountain Health Care, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- AVANDAMET
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Jan 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Coronary Artery Disease
- Being tested
- AVANDAMET
- Keywords
- rosiglitazone, metformin, hs-CRP, inflammation
- Medical subject headings
- Coronary Artery Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVANDAMETDrug
2/500 mg
| Study group | Role | What they receive |
|---|---|---|
| Avandamet | Active comparator | AVANDAMET 2/500 mg Receives: Drug: AVANDAMET |
| Placebo | Placebo comparator | Not described Receives: Drug: AVANDAMET |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein.
Measured: Study completion
To demonstrate the safety of the interventions on clinical outcomes (death, MI, cardiovascular hospitalizations) and serious drug-related adverse events.
Measured: Study completion
Secondary outcomes (5)
To demonstrate the effect (change from baseline) of each study intervention on lipid levels
Measured: Study completion
To demonstrate the effect (change from baseline) of each study intervention on inflammatory marker levels other than hs-CRP
Measured: Study completion
To demonstrate the effect (change from baseline) of each study intervention on HgbA1C
Measured: Study completion
To demonstrate the effect (change from baseline) of each study intervention on fasting blood glucose
Measured: Study completion
Safety: Differences in adverse events between the two arms
Measured: Interim; completion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2006 (estimated)
- Study startJun 2006
- Primary completionNov 2007
- Study completionJan 2008
Why it stopped: FDA concerns regarding Avandamet
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- Joseph B Muhlestein, MD, Principal investigator, Intermountain Healthcare, LDS Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00343395
- Sponsor's protocol ID
- 128-013
- Status last verified
- Mar 2011
- First submitted
- 21 Jun 2006
- Last updated
- 17 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00343395
- Acronym / sponsor ID
- 128-013
- Conditions
- Coronary Artery Disease
- Keywords
- rosiglitazone, metformin, hs-CRP, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: FDA concerns regarding Avandamet
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jun 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 23 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Avandamet | Active comparator | Drug: AVANDAMETAVANDAMET 2/500 mg |
| Placebo | Placebo comparator | Drug: AVANDAMET |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVANDAMET2/500 mg | Drug | Avandamet, Placebo |
Primary outcome
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
5 secondary outcomes
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
Results and safety
The study was stopped early (reason given: FDA concerns regarding Avandamet). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2011.
Related trials for Coronary Artery Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph B Muhlestein, MD principal investigator
Intermountain Healthcare, LDS Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing AVANDAMET in people with Coronary Artery Disease, run by Intermountain Health Care, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: FDA concerns regarding Avandamet). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To demonstrate the effect (change from baseline) of each study intervention on hs-C-reactive protein. (time frame: Study completion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2011.