Vein-Coronary Atherosclerosis And Rosiglitazone After Bypass Surgery: The VICTORY Trial

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Laval University
ClinicalTrials.gov Identifier:
NCT00169832
First received: September 12, 2005
Last updated: October 9, 2008
Last verified: October 2008
  Purpose

HYPOTHESES

  • Rosiglitazone in diabetic patients with previous coronary bypass surgery may prevent or slow the progression of atherosclerosis in SVGs and native coronary arteries.
  • Rosiglitazone has favorable effects on adipose tissue distribution variables as well as on thrombosis, pro-inflammatory, and lipid profiles in diabetic patients after coronary bypass artery surgery.
  • Rosiglitazone therapy influences favorably metabolism and clinical outcomes in diabetic patients after coronary artery bypass surgery.

OBJECTIVES

  • PRIMARY To assess the efficacy of rosiglitazone to reduce atherosclerosis progression in vein grafts in diabetic patients after coronary bypass surgery by using IVUS imaging after a 12 mo follow-up.
  • SECONDARY

    • To prospectively compare the secondary IVUS endpoints.
    • To prospectively compare the angiographic endpoints.
    • To prospectively compare the metabolic risk factor endpoints.
    • To prospectively compare the body composition and distribution endpoints.
    • To prospectively compare the clinical outcomes of rosiglitazone versus standard care using composite endpoints.

Condition Intervention Phase
Diabetes
Coronary Artery Bypass Grafting
Drug: Rosiglitazone or placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Multicenter Randomized Double-Blind Trial Comparing Rosiglitazone to Placebo for the Prevention of Atherosclerosis Progression After Coronary Bypass Surgery in Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in plaque volume in one SVG (by IVUS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1 Change in plaque volume in segment of anastomosed coronary artery [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 2 Changes in lumen and total vessel volumes and lumen plaque total vessel areas in SVG and coronary segments [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 3 Changes in qualitative plaque characterization in the SVG and coronary segments [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 4 Patients showing atherosclerosis changes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 5 Atherosclerosis changes concordance and discordance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 6 New occlusions in native coronary arteries or SVGs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 7 Changes in reference and minimum lumen diameters of the SVG [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 8 Per patient percentage of initially patent SVGs that had significant progression of atherosclerosis at the site of greatest change at follow-up [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 9 Changes of indices for comprehensive lipid thrombosis and pro-inflammatory profiles as well as glucose-insulin homeostasis, microalbuminuria, adhesion molecules, adipokines, and other markers relevant to the evaluation and management of cardiovascular [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 10 Changes in abdominal areas and volumes of adipose tissue areas [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 11 Changes in body composition, body weight, waist circumference and BMI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 12 Clinical laboratory parameters, physical examinations, vital signs, ECGs, concomitant medication and adverse events [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 13 Death, MI, TIA, stroke, hospitalization and ischemia-driven interventions [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 14 Fluid retention [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 193
Study Start Date: June 2003
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosiglitazone (Avandia) Drug: Rosiglitazone or placebo
Rosiglitazone 4 to 8 mg/day or placebo, for 12 months
Other Name: Avandia
Placebo Comparator: Placebo Drug: Rosiglitazone or placebo
Rosiglitazone 4 to 8 mg/day or placebo, for 12 months
Other Name: Avandia

Detailed Description:

STUDY DESIGN

This is a prospective multicenter randomized placebo-controlled double-blind trial assessing the efficacy and safety of rosiglitazone in the prevention of atherosclerosis progression in vein grafts and native coronary arteries of diabetic patients. Stable diabetic patients with previous coronary bypass surgery (≥ 1 year ≤ 10 years) will be screened. After baseline evaluation, all eligible patients will undergo baseline coronary angiogram. IVUS will be performed in a segment length of at least 40 mm in a SVG suitable for IVUS analysis and in a segment length of at least 20 mm in the anastomosed native coronary artery corresponding to the SVG chosen. Following the IVUS procedure, patients will be randomized to either rosiglitazone treatment or to placebo in addition to their standard clinical care. Study drug will be titrated over an 8-week period up to a dose of 8 mg/day (or to maximum tolerated dose). The patients will receive the study drug or the placebo for 50-54 weeks in a double-blind manner. At the beginning and at 2, 4, 6, 8, 10 and 12 months of treatment, patients will be subjected to a set of morphological, physiological and metabolic evaluations. At the final visit (12 months), patients will also be submitted to IVUS and angiography.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

AT SCREENING:

  1. Male or female, aged ≥ 40 years & ≤ 75 years.
  2. Women of childbearing potential with contraceptive measure, or of non-childbearing potential or surgically sterile.
  3. Type 2 diabetes mellitus.
  4. Patients with no new medication for hyperglycemia and no change in dose of oral hypoglycemic medication within the last 3 mo prior to screening.
  5. Diabetic patients with ischemic heart disease and CABG with at least one SVG (≥1 yr & ≤10 yrs).
  6. Patient agrees to participate.
  7. Patient legally capable of giving consent and understand what participation in study entails, potential risks and benefits, freedom to withdraw without any prejudice to subsequent medical arrangement or treatment, sign an ICF prior to any protocol specific procedure.

AT IVUS & ANGIOGRAPHY (VISIT 2):

Subject eligible if at least 1), 2) and 3) of the following criteria apply:

  1. Patient with at least 1 patent SVG.
  2. Segment length of at least 40 mm in SVG suitable for IVUS.
  3. Reference of target (SVG) diameter ≥ 2.5 mm.

    If anastomosed native coronary artery or non grafted coronary artery can be evaluated, the following criteria must be met:

  4. Reference of target anastomosed native coronary artery or non grafted coronary artery diameter≥ 2.5 mm.
  5. Segment length of at least 20 mm in anastomosed native coronary artery corresponding to SVG chosen or, in case of impossibility of performing IVUS in the anastomosed coronary artery, a non grafted coronary artery (≥ 30 mm length segment) might be used for reference.

Exclusion Criteria:

AT SCREENING:

  1. Clinically significant abnormality at screening tests & exams.
  2. Type 1 diabetes or history of diabetic ketoacidosis.
  3. Uncontrolled type 2 diabetes mellitus.
  4. Recent MI or ACS (≤ 90 days).
  5. History of hypersensitivity to thiazolidinediones (TZD) or compounds of similar chemical structures.
  6. Last LVEF≤ 35%.
  7. SBP>170mmHg or DBP>100mmHg at screening/baseline should be appropriately treated and under control prior to randomization.
  8. Unstable or Canadian Cardiovascular Society class III and IV angina, acute heart failure or congestive heart failure (NYHA class III and IV).
  9. History of hepatocellular reaction/severe oedema/other potentially fluid-related AE associated with use of any TZD or PPAR-γ agonist.
  10. Hepatic disease.
  11. Renal dysfunction.
  12. Anemia.
  13. TG ≥ 10 mmol/L.
  14. History of PCI in all SVG(s).
  15. Known occlusion(s) of all SVG(s).
  16. Treatment involving TZD within 3 mo prior to screening.
  17. Chronic use (≥ 6 mo) of insulin for glycemic control at any time in the past or administration of insulin any time within the last 12 mo.
  18. Allergy to contrast agents.
  19. Current intake of anorectic agents or have been taken off an anorectic agent or equivalent within 3 mo prior to screening.
  20. Patients for whom oral or injectable corticosteroids are used on a regular or recurrent basis.
  21. Recent history/suspicion of current drug abuse or alcohol abuse within last 6 mo.
  22. Women breast feeding, pregnant, or planning to become pregnant during conduct of trial and for 30 days after study completion.
  23. Other illness that precludes survival.
  24. History of malignancy within the last 5 yrs.
  25. Concurrent participation in other investigational device or drug studies and/or having received any experimental therapeutic agents within 30 days of the screening.
  26. Use of any investigational drug for glycemic control within 3 mo of the screening.
  27. Patient travelling out of town/country for periods exceeding 2 mo.
  28. Medical condition which may interfere with intake and/or absorption of study medication.
  29. Patients unwilling or unable to comply with procedures.
  30. Recent major surgery within 90 days of the screening.

AT IVUS AND ANGIOGRAPHY (VISIT 2):

  1. PCI was performed on the target segment(s) after CABG.
  2. Target SVG and/or target native coronary artery show ≥ 50% angiographic lesion precluding IVUS.
  3. Thrombus/thrombus aspect in target vessels.
  4. Target vessel has been subjected to surgical endarterectomy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00169832

Locations
Canada, Nova Scotia
QEII Health Sciences Center - Halifax Infirmary
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Hamilton Health Sciences - Mc Master Clinic
Hamilton, Ontario, Canada, L8L 2X2
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
CRMSBC
Bonaventure, Quebec, Canada, G0C 1E0
CHUM Notre-Dame Hospital
Montreal, Quebec, Canada, H2L 4M1
Laval Hospital
Sainte-Foy, Quebec, Canada, G1V 4G5
Spain
Hospital Universitari Vall D'Hebron
Barcelona, Spain
Hospital Del Mar
Barcelona, Spain
Hospital Universitarion Son Dureta
Palma de Mallorca, Spain
Sponsors and Collaborators
Laval University
GlaxoSmithKline
Investigators
Principal Investigator: Olivier F Bertrand, MD, PhD Laval Hospital Research Center
Principal Investigator: Jean-Pierre Despres, PhD Laval Hospital Research Center
Principal Investigator: Paul Poirier, MD, PhD Laval Hospital Research Center
  More Information

No publications provided by Laval University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Olivier F Bertrand, MD PhD, Hopital Laval
ClinicalTrials.gov Identifier: NCT00169832     History of Changes
Other Study ID Numbers: 49653/416, ISRCTN54136716
Study First Received: September 12, 2005
Last Updated: October 9, 2008
Health Authority: Canada: Health Canada

Keywords provided by Laval University:
Atherosclerosis progression
Ischemic heart disease
Saphenous vein graft
Metabolic risk factors
Rosiglitazone

Additional relevant MeSH terms:
Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014