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
Study complete
Study complete
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:
Enrollment:
672
Primary completion date:
2008-08-08
Observational study model:
Not applicable
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
- Inclusion criteria:
- Male or female between 30 to 80 years of age, inclusive.
Inclusion and exclusion criteria
Inclusion 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
Showing 1 - 6 of 153 Results
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
Study complete
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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