Last updated: 11/04/2018 05:17:22
Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Phase III, 18 Month, Multicenter, Randomized, Double-Blind, Active-Controlled Clinical Trial to Compare Rosiglitazone versus Glipizide on the Progression of Atherosclerosis in Subjects with Type 2 Diabetes Mellitus and Cardiovascular Disease (APPROACH)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in Percent Atheroma Volume (PAV) to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Percent Atheroma Volume (PAV) to Month 18
Timeframe: Baseline to Month 18
Secondary outcomes:
Change from Baseline in Atheroma, Vessel, and Lumen Volume to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Atheroma Volume to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Lumen Volume to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Vessel Volume to Month 18
Timeframe: Baseline to Month 18
Change from Baseline in Atheroma, Vessel, and Lumen Area to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Atheroma Area to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Lumen Area to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Vessel Area to Month 18
Timeframe: Baseline to Month 18
Change from Baseline in Normalized Atheroma Volume
Timeframe: Baseline to Month 18
Model Adjusted Change from Baseline in Normalized Atheroma Volume
Timeframe: Baseline to Month 18
Change in Atheroma Volume within the 10 mm of the Non-intervened Vessel Segment with the Greatest Atheroma Volume at Baseline
Timeframe: Baseline to Month 18
Model Adjusted Change in Atheroma Volume within the 10 mm of the Non-intervened Vessel Segment with the Greatest Atheroma Volume at Baseline
Timeframe: Baseline to Month 18
Change in Atheroma Area within the 10 mm of the Non-intervened Vessel Segment with the Greatest Atheroma Volume at Baseline
Timeframe: Baseline to Month 18
Model Adjusted Change in Atheroma Area within the 10 mm of the Non-intervened Vessel Segment with the Greatest Atheroma Volume at Baseline
Timeframe: Baseline to Month 18
Model Adjusted Change in Glycated hemoglobin (HbA1c) from Baseline to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Change in Fasting Plasma Glucose (FPG) from Baseline to Month 18
Timeframe: Baseline to Month 18
Repeated Measures Analysis of Percent Change in hsCRP from Baseline to Month 18
Timeframe: Baseline to Month 18
Repeated Measures Analysis of Percent Change in MMP 9 from Baseline to Month 18
Timeframe: Baseline to Month 18
Percent Change in Brain Natriuretic Peptide (BNP) from Baseline to Month 18
Timeframe: Baseline to Month 18
Model Adjusted Percent Change in Brain Natriuretic Peptide (BNP) from Baseline to Month 18
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in total cholesterol (TC)
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in high density lipoprotein cholesterol (HDL-c)
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in HDL-2
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in HDL-3
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in low density lipoprotein cholesterol (LDL-c)
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in Triglycerides (TG)
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in Free Fatty Acids (FFA)
Timeframe: Baseline to Month 18
Percent Change from Baseline to Month 18 in apoprotein B (apoB)
Timeframe: Baseline to Month 18
Change from Baseline to Month 18 in LDL-c peak particle density measured by LDL relative flotation
Timeframe: Baseline to Month 18
Change from Baseline to Month 18 in Total Cholesterol/HDL-c Ratio
Timeframe: Baseline to Month 18
Change from Baseline to Month 18 in LDL-c/HDL-c Ratio
Timeframe: Baseline to Month 18
Number of Participants with the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for all-cause death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for recurrent myocardial ischemia (MACE Composite 1)
Timeframe: Baseline to Month 21
Number of Participants with the Indicated Treatment Emergent Major Cardiovascular Events (MACE) for cardiovascular death, nonfatal MI, or nonfatal stroke (MACE Composite 2)
Timeframe: Baseline to Month 21
Number of Other Cardiovascular Events
Timeframe: Baseline to Month 21
Interventions:
Drug: Glipizide
Drug: rosiglitazone maleate
Enrollment:
672
Observational study model:
Not applicable
Primary completion date:
2008-08-08
Time perspective:
Not applicable
Clinical publications:
García-García H, Garg S, Brugaletta S, Morocutti G, Ratner R, Kolatkar N, Kravitz B, Miller D, Huang C,. Nesto R, Serruys P, and the 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) Running title: In-stent restenosis in the APPROACH trial . [Int J Cardiovasc Imaging]. 2011;Feb 27(.):Epub ahead of print .
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).
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)
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):1074-1079.
Medical condition
Atherosclerosis
Product
rosiglitazone
Collaborators
Not applicable
Study date(s)
January 2005 to August 2008
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
30 - 80 years
Accepts healthy volunteers
No
- 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).
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
- Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgement of the Investigator, would preclude safe completion of the study.
- Blood pressure: SBP >170 or DBP > 100 mmHg
- Significant anemia (Hemoglobin < 11 g/dL for males and < 10 g/dL for females).
- Significant renal disease manifested by serum creatinine (> 1.5mg/dL for males or > 1.4mg/dL for females), or where the use of metformin is contra-indicated.
- Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 2.5 times upper limit of normal (ULN) or bilirubin >2x ULN).
- History of myopathy or history of elevated creatine kinase (CK) > 3 times upper normal limit.
- Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer).
- Women who are lactating, pregnant or planning to become pregnant during the course of the study.
- Unwillingness or inability to comply with the procedures described in this protocol.
Trial location(s)
Location
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68161
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Springfield, Massachusetts, United States, 01199
Status
Study Complete
Location
GSK Investigational Site
Dormagen, Nordrhein-Westfalen, Germany, 41539
Status
Study Complete
Location
GSK Investigational Site
Rhaunen, Rheinland-Pfalz, Germany, 55624
Status
Study Complete
Location
GSK Investigational Site
Tucson, Arizona, United States, 85745
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Springfield, Illinois, United States, 62702
Status
Study Complete
Location
GSK Investigational Site
Torrance, California, United States, 90509
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, 1416
Status
Study Complete
Location
GSK Investigational Site
Corpus Christi, Texas, United States, 78404
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45355
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Canton, Ohio, United States, 44708
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dortmund, Nordrhein-Westfalen, Germany, 44328
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Scottsdale, Arizona, United States, 85251
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dortmund, Nordrhein-Westfalen, Germany, 44339
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45136
Status
Study Complete
Location
GSK Investigational Site
Milwaukee, Wisconsin, United States, 53215
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Sr. Ingbert, Saarland, Germany, 66386
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46260
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ludwigshafen, Rheinland-Pfalz, Germany, 67063
Status
Study Complete
Location
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina, 1181
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ribeirão Preto, São Paulo, Brazil, 14048-900
Status
Study Complete
Location
GSK Investigational Site
Kulmbach, Bayern, Germany, 95326
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45329
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21287
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45309
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Gelsenkirchen, Nordrhein-Westfalen, Germany, 45881
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, B1704ETD
Status
Study Complete
Location
GSK Investigational Site
Camp Hill, Pennsylvania, United States, 17011
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Antonio, Texas, United States, 78207
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95825
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, 1405
Status
Study Complete
Location
GSK Investigational Site
Marl, Nordrhein-Westfalen, Germany, 45772
Status
Study Complete
Location
GSK Investigational Site
Huntington Beach, California, United States, 92648
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mission Viejo, California, United States, 92691
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dinslaken, Nordrhein-Westfalen, Germany, 46537
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Speyer, Rheinland-Pfalz, Germany, 67346
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44789
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Englewood, Colorado, United States, 80113
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20010
Status
Study Complete
Location
GSK Investigational Site
Beaver, Pennsylvania, United States, 15009
Status
Terminated/Withdrawn
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 05651-901
Status
Study Complete
Location
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47119
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bellevue, Washington, United States, 98004
Status
Study Complete
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69126
Status
Terminated/Withdrawn
Location
GSK Investigational Site
NIEUWEGEIN, Netherlands, 3435 CM
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, 1221
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19141
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30309
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Trier, Rheinland-Pfalz, Germany, 54296
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80220
Status
Study Complete
Location
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27157
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40454
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Moron-Provincia de Buenos Aires, Argentina, 1709
Status
Study Complete
Location
GSK Investigational Site
Luenen, Nordrhein-Westfalen, Germany, 44534
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
Status
Study Complete
Location
GSK Investigational Site
San Justo, Buenos Aires, Argentina, B7118XAB
Status
Study Complete
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 04012-909
Status
Study Complete
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 05403-000
Status
Study Complete
Location
GSK Investigational Site
Friedrichsthal, Saarland, Germany, 66299
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Status
Study Complete
Location
GSK Investigational Site
Monterrey, Nuevo León, Mexico, 64060
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44653
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Peoria, Illinois, United States, 61615
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Leverkusen, Nordrhein-Westfalen, Germany, 51377
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95817
Status
Will Be Recruiting
Location
GSK Investigational Site
Trier, Rheinland-Pfalz, Germany, 54292
Status
Study Complete
Location
GSK Investigational Site
Springfield, Missouri, United States, 65807
Status
Study Complete
Location
GSK Investigational Site
Albany, New York, United States, 12208
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Montreal, Québec, Canada, H1T 1C8
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New Brunswick, New Jersey, United States, 08903
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Columbia, Maryland, United States, 21044
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Udine, Friuli-Venezia-Giulia, Italy, 33100
Status
Study Complete
Location
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina, C1155ADP
Status
Study Complete
Location
GSK Investigational Site
Le Plessis Robinson, France, 92350
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dortmund, Nordrhein-Westfalen, Germany, 44137
Status
Study Complete
Location
GSK Investigational Site
San Martín, Buenos Aires, Argentina, 1650
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1416DRW
Status
Study Complete
Location
GSK Investigational Site
Burbank, California, United States, 91505
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Melbourne, Florida, United States, 32901
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35235
Status
Study Complete
Location
GSK Investigational Site
Oberhausen, Nordrhein-Westfalen, Germany, 46049
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90017
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Torrance, California, United States, 90503
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jackson, Tennessee, United States, 38301
Status
Study Complete
Location
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44623
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2008-08-08
Actual study completion date
2008-08-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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