Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes

NCT00116831 | Completed Phase 3 Results DMC

• 1 other identifier: AVD100521
• Study Type: interventional
• Target: 672
• Locations: 20 countries
• Sites: 156

Brief Summary

The purpose of this study is to test the safety and effectiveness of rosiglitazone against a sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels of the heart.

Conditions

Atherosclerosis

Keywords

atheroma; IVUS; Intravascular ultrasound; atherosclerosis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Percent Atheroma Volume (PAV) to Month 18

  The primary efficacy endpoint was change in PAV (defined as total atheroma volume divided by total vessel volume x 100) within a 40 mm segment in non-intervened coronary arteries from Baseline to Month 18, based upon Intravascular Ultrasound (IVUS) assessment.

  Baseline to Month 18

• Model Adjusted Change From Baseline in Percent Atheroma Volume (PAV) to Month 18

  Model Adjusted Change (MAC) = Baseline + Region + Sex + Treatment + Cardiac Procedure + Prior Oral Anti-Hyperglycemic Diabetic Medications(s) (OAD).

  Baseline to Month 18

Secondary Outcomes (34)

• Change From Baseline in Atheroma, Vessel, and Lumen Volume to Month 18

  Baseline to Month 18

• Model Adjusted Change From Baseline in Atheroma Volume to Month 18

  Baseline to Month 18

• Model Adjusted Change From Baseline in Lumen Volume to Month 18

  Baseline to Month 18

• Model Adjusted Change From Baseline in Vessel Volume to Month 18

  Baseline to Month 18

• Change From Baseline in Atheroma, Vessel, and Lumen Area to Month 18

  Baseline to Month 18

Study Arms (2)

Glipizide

ACTIVE COMPARATOR

oral anti-diabetic medication

Drug: Glipizide

rosiglitazone maleate

EXPERIMENTAL

oral anti-diabetic medication

Drug: rosiglitazone maleate

Interventions

Glipizide DRUG

oral anti-diabetic medication

Glipizide

rosiglitazone maleate DRUG

oral antidiabetic medication

rosiglitazone maleate

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 30 to 80 years of age, inclusive.
• Established diagnosis of T2DM (based on diagnostic criteria of the American Diabetes Association (ADA), WHO guidelines or local national guidelines).
• Subjects who are undergoing coronary angiography for evaluation of suspected or previously diagnosed coronary artery disease or who are undergoing PCI.
• Subjects' prior anti-hyperglycemic diabetic therapy:
• Diet and exercise only (drug naïve), with HbA1c \>7.0 and £ 10.0%. HbA1c \> 6.5 and \<= 8.5%.
• Left ventricular ejection fraction (EF) ³ 40% as assessed by contrast ventriculography (or previously documented in medical notes within one month prior to index procedure by other methods e.g. echocardiography or nuclear study)
• Female subjects must be postmenopausal (i.e., \>6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, Norplant, Depo-Provera, an intra-uterine device (IUD), a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1a, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study medication.
• Willingness and ability to give informed consent prior to entering the study and available to complete the study.

You may not qualify if:

• Type 1 diabetes and/or history of diabetic ketoacidosis.
• Exposure to a TZD or other PPAR-g agonist within the 6 months prior to screening visit.
• Subjects treated with triple OAD therapy or high dose dual combination OAD therapy \[1\].
• Subjects who have required chronic insulin use in the last 6 months (except during pregnancy or acute episodes such as hospitalization, trauma or infection).
• ST segment elevation myocardial infarction in the last 30 days.
• Subjects who have a history or are scheduled to receive coronary artery bypass graft surgery (CABG), valve repair or replacement, aneurysmectomy or planned major non-cardiac surgery during the study period.
• Subjects who have severe cardiac valvular disease
• Stroke or resuscitated in the past 6 months
• History of congestive heart failure (NYHA class I - IV)
• History of significant hypersensitivity or reaction (e.g., difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to any TZD, SU, biguanide or insulin
• Prior history of severe edema or edema requiring medical treatment.
• Chronic disease requiring chronic or intermittent treatment with oral, intravenous, or injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible).
• Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months.
• Untreated hypo- or hyperthyroidism
• A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (156)

GSK Investigational Site

Birmingham, Alabama, 35235, United States

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GSK Investigational Site

Scottsdale, Arizona, 85251, United States

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Tucson, Arizona, 85745, United States

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Burbank, California, 91505, United States

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Huntington Beach, California, 92648, United States

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Los Angeles, California, 90017, United States

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Mission Viejo, California, 92691, United States

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Sacramento, California, 95817, United States

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GSK Investigational Site

Sacramento, California, 95825, United States

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Torrance, California, 90503, United States

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Torrance, California, 90509, United States

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Denver, Colorado, 80220, United States

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Englewood, Colorado, 80113, United States

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Washington D.C., District of Columbia, 20010, United States

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Melbourne, Florida, 32901, United States

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Tampa, Florida, 33609, United States

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Atlanta, Georgia, 30309, United States

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Peoria, Illinois, 61615, United States

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Springfield, Illinois, 62702, United States

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Indianapolis, Indiana, 46260, United States

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Baltimore, Maryland, 21287, United States

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Columbia, Maryland, 21044, United States

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Springfield, Massachusetts, 01199, United States

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Springfield, Missouri, 65807, United States

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New Brunswick, New Jersey, 08903, United States

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Albany, New York, 12208, United States

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New York, New York, 10032, United States

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Winston-Salem, North Carolina, 27103, United States

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Winston-Salem, North Carolina, 27157, United States

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Canton, Ohio, 44708, United States

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Beaver, Pennsylvania, 15009, United States

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Camp Hill, Pennsylvania, 17011, United States

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Philadelphia, Pennsylvania, 19141, United States

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Jackson, Tennessee, 38301, United States

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Corpus Christi, Texas, 78404, United States

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San Antonio, Texas, 78207, United States

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San Antonio, Texas, 78229, United States

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Bellevue, Washington, 98004, United States

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Milwaukee, Wisconsin, 53215, United States

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Capital Federal, Buenos Aires, 1181, Argentina

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Capital Federal, Buenos Aires, C1155ADP, Argentina

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Capital Federal, Buenos Aires, C1437JCP, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, B1704ETD, Argentina

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Munro, Buenos Aires, 1605, Argentina

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San Justo, Buenos Aires, B7118XAB, Argentina

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San Martín, Buenos Aires, 1650, Argentina

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Córdoba, Córdoba Province, 5000, Argentina

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Buenos Aires, 1221, Argentina

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Buenos Aires, 1405, Argentina

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Buenos Aires, 1416, Argentina

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Buenos Aires, 1428, Argentina

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Buenos Aires, C1416DRW, Argentina

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Córdoba, 5000, Argentina

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Moron-Provincia de Buenos Aires, 1709, Argentina

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Ribeirão Preto, São Paulo, 14048-900, Brazil

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São Paulo, São Paulo, 04012-909, Brazil

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São Paulo, São Paulo, 05403-000, Brazil

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São Paulo, São Paulo, 05651-901, Brazil

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Hamilton, Ontario, L8L 2X2, Canada

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London, Ontario, N6A 4V2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H1T 1C8, Canada

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Hradec Králové, 500 05, Czechia

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Corbeil-Essonnes, 91106, France

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Le Plessis-Robinson, 92350, France

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Marseille, 13005, France

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Rennes, 35033, France

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Heidelberg, Baden-Wurttemberg, 69126, Germany

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Mannheim, Baden-Wurttemberg, 68161, Germany

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Coburg, Bavaria, 96450, Germany

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Kronach, Bavaria, 96317, Germany

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Kulmbach, Bavaria, 95326, Germany

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Lichtenfels, Bavaria, 96215, Germany

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Hirschhorn, Hesse, 69434, Germany

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Lampertheim, Hesse, 68623, Germany

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Bochum, North Rhine-Westphalia, 44789, Germany

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Dinslaken, North Rhine-Westphalia, 46537, Germany

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Dormagen, North Rhine-Westphalia, 41539, Germany

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Dortmund, North Rhine-Westphalia, 44137, Germany

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Dortmund, North Rhine-Westphalia, 44328, Germany

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Dortmund, North Rhine-Westphalia, 44339, Germany

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Duisburg, North Rhine-Westphalia, 47119, Germany

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Düsseldorf, North Rhine-Westphalia, 40454, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Essen, North Rhine-Westphalia, 45136, Germany

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Essen, North Rhine-Westphalia, 45309, Germany

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Essen, North Rhine-Westphalia, 45329, Germany

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Essen, North Rhine-Westphalia, 45355, Germany

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Essen, North Rhine-Westphalia, 45359, Germany

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Gelsenkirchen, North Rhine-Westphalia, 45881, Germany

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Herne, North Rhine-Westphalia, 44623, Germany

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Herne, North Rhine-Westphalia, 44653, Germany

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Leverkusen, North Rhine-Westphalia, 51377, Germany

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Lünen, North Rhine-Westphalia, 44534, Germany

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Marl, North Rhine-Westphalia, 45772, Germany

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Oberhausen, North Rhine-Westphalia, 46049, Germany

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Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany

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Rhaunen, Rhineland-Palatinate, 55624, Germany

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Speyer, Rhineland-Palatinate, 67346, Germany

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Trier, Rhineland-Palatinate, 54292, Germany

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Trier, Rhineland-Palatinate, 54296, Germany

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Friedrichsthal, Saarland, 66299, Germany

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GSK Investigational Site

Saarlouis, Saarland, 66740, Germany

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Sr. Ingbert, Saarland, 66386, Germany

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Athens, 115 26, Greece

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Athens, 115 27, Greece

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Athens, 155 62, Greece

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Athens, 176 74, Greece

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Causeway Bay, Hong Kong

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Kowloon, Hong Kong

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GSK Investigational Site

Kwun Tong, Hong Kong

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Pokfulam, Hong Kong

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Shatin, Hong Kong

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Mumbai, 400005, India

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New Delhi, 110017, India

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Udine, Friuli Venezia Giulia, 33100, Italy

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Rozzano (Mi), Lombardy, 20089, Italy

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Riga, LV1002, Latvia

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Guadalajara, Jalisco, 44340, Mexico

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Monterrey, Nuevo León, 64060, Mexico

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Breda, 4818 CK, Netherlands

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Eindhoven, 5623 EJ, Netherlands

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Enschede, 7511JX, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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Rotterdam, 3015 GD, Netherlands

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Rotterdam, 3075 EA, Netherlands

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Zwolle, 8011 JW, Netherlands

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Bialystok, 15-276, Poland

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Kalisz, 62-800, Poland

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Katowice, 40-635, Poland

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Poznan, 60-355, Poland

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Warsaw, 04-628, Poland

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Moscow, 105 229, Russia

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GSK Investigational Site

Moscow, 121552, Russia

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GSK Investigational Site

Moscow, 123182, Russia

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GSK Investigational Site

Seoul, 110-744, South Korea

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GSK Investigational Site

Seoul, 120-752, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Suwon, 443-721, South Korea

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GSK Investigational Site

Alicante, 03010, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 08097, Spain

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GSK Investigational Site

Madrid, 28035, Spain

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GSK Investigational Site

Marid, 28040, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Murcia, 30120, Spain

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GSK Investigational Site

Oviedo, 33006, Spain

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GSK Investigational Site

San Juan/Alicante, 03550, Spain

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GSK Investigational Site

Gothenburg, SE-413 45, Sweden

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GSK Investigational Site

Stockholm, SE-171 76, Sweden

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GSK Investigational Site

Bangkok, 10330, Thailand

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GSK Investigational Site

Chiang Mai, 50200, Thailand

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Related Publications (5)

• Garcia-Garcia HM, Garg S, Brugaletta S, Morocutti G, Ratner RE, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Nesto RW, Serruys PW; APPROACH study group. Evaluation of in-stent restenosis in the APPROACH trial (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History). Int J Cardiovasc Imaging. 2012 Mar;28(3):455-65. doi: 10.1007/s10554-011-9836-z. Epub 2011 Feb 27.

  PMID: 21359834 BACKGROUND

• Gerstein HC, Ratner RE, Cannon CP, Serruys PW, García-García HM, van Es G-A, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Fitzgerald PJ, Nesto RW; APPROACH study group. Effect of Rosiglitazone on Progression of Coronary Atherosclerosis in Patients with Type 2 Diabetes and Coronary Artery Disease: The APPROACH trial. (Submitted for publication).

  BACKGROUND

• Nesto RW. Effect of rosiglitazone versus glipizide on progression of coronary atherosclerosis in patients with type 2 diabetes and coronary artery disease. American Heart Association Scientific Sessions. November 12, 2008, New Orleans, LA. (http://directnews.americanheart.org/extras/pdfs/approach_slides.pdf)

  BACKGROUND

• Ratner RE, Cannon CP, Gerstein HC, Nesto RW, Serruys PW, Van Es GA, Kolatkar NS, Kravitz BG, Zalewski A, Fitzgerald PJ; APPROACH Study Group. Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics. Am Heart J. 2008 Dec;156(6):1074-9. doi: 10.1016/j.ahj.2008.07.025. Epub 2008 Oct 11.

  PMID: 19033001 BACKGROUND

• Gerstein HC, Ratner RE, Cannon CP, Serruys PW, Garcia-Garcia HM, van Es GA, Kolatkar NS, Kravitz BG, Miller DM, Huang C, Fitzgerald PJ, Nesto RW; APPROACH Study Group. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation. 2010 Mar 16;121(10):1176-87. doi: 10.1161/CIRCULATIONAHA.109.881003. Epub 2010 Mar 1.

  PMID: 20194881 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Atherosclerosis; Plaque, Atherosclerotic

Interventions

Glipizide; Rosiglitazone

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazolidinediones; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2005
• First Posted: July 1, 2005
• Study Start: January 1, 2005
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: March 23, 2017
• Results First Posted: March 31, 2010

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

ME (2); NL (7); DE (38); KR (4); SE (2); FR (4); HK (5); GR (4); ES (11); BR (4); PL (5); CA (5); LA (1); RU (3); US (39); AR (15); CZ (1); IT (2); TH (2); IN (2)