AVANDIA CV Outcomes Study: Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) A Multicenter Randomized Double-Blind Placebo-Controlled Trial of a Thiazolidinedione or Placebo and of Vitamin D or Placebo In People With Type 2 Diabetes at Risk For Cardiovascular Disease
Overview
- Phase
- Phase 4
- Intervention
- pioglitazone
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1332
- Locations
- 1
- Primary Endpoint
- Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
This study will answer two separate questions.
The first question is to test the cardiovascular effects of long-term treatment with rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease.
The second question will compare the effects of long-term supplementation of vitamin D on death and cancer
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) greater than or equal to 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
- •Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening
- •Age ≥ 50 years and evidence of vascular disease defined as ≥1of:
- •prior myocardial infarction
- •prior stroke
- •coronary, carotid or peripheral artery revascularization ≥ 4 years earlier
- •previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation OR
- •Age ≥ 55 years and evidence of subclinical vascular disease defined as ≥1 of:
- •microalbuminuria or proteinuria
- •history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ECG) or echocardiogram
Exclusion Criteria
- •Type 1 diabetes
- •Current need for insulin treatment
- •Symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician
- •An acute cardiovascular event within 30 days prior to randomization
- •Symptomatic heart failure (i.e. New York Heart Association class II or higher) or any episode of previous pulmonary edema or known ejection fraction \< 0.4 or current use of loop diuretics
- •Any fracture within the past 1 year
- •Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery
- •Coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, MI, or stroke in the intervening period
- •End stage renal disease requiring renal replacement therapy
- •Receiving drug therapy to treat liver disease
Arms & Interventions
pioglitazone
PIO tablet was administered in the dose of 30 milligrams (mg) OD initially and could be titrated to a maximum dose of 45 mg at or after the 6-month visit. After 1 year of treatment, the dose of PIO was increased to 45 mg OD for the duration of 5.5 years.
Intervention: pioglitazone
rosiglitazone
RSG tablet was administered in the dose of 4 mg OD initially and could be titrated to a maximum dose of 8 mg at or after the 6-month visit. After 1 year of treatment, the dose of RSG was increased to 8 mg OD for the duration of 5.5 years.
Intervention: rosiglitazone
TZD placebo
Matching placebo tablet was administered once a day (OD) for the duration of 5.5 years
Intervention: Placebo
Vitamin D
Active comparator
Intervention: Vitamin D
Vitamin D placebo
Placebo Comparator
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)
Time Frame: From Randomization at Visit 3 up to the Final Visit (average of 162 days)
An event adjudication committee (EAC) adjudicated all occurrences of the components of the composite cardiovascular (CV; related to heart) outcome for TZD. Components are the first occurrence of cardiovascular death for which a non-heart-related cause has not been identified; non-fatal myocardial infarction (MI) (death of heart muscle from sudden blockage of a coronary artery by blood clot not leading to death); and non-fatal stroke (rapidly developing loss of brain function\[s\] due to disturbance in the blood supply to the brain not leading to death).
Number of Participants With the Indicated Components of the Composite Outcome for Vitamin D
Time Frame: From Randomization at Visit 3 to Final Visit (up to 162 days)
An EAC adjudicated all occurrences of the components of the composite outcome for vitamin D. Components are the first occurrence of death or cancer requiring hospitalization, treatment with medicines (chemotherapy), or surgery.
Secondary Outcomes
- Number of Participants With Any Revascularization(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Need for Hospitalization for Any Reason(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Need for Hospitalization for Congestive Heart Failure (CHF), Shortness of Breath, Pneumonia, or Angina(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Composite Microvascular Outcome(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Retinopathy Requiring Laser Therapy, a Decline in Estimated Glomerular Filtration Rate (eGFR), Vitrectomy, and Renal Replacement Therapy(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Severe Lower Than Normal Blood Glucose Level (Hypoglycemia)(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Clinical Proteinuria(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With a Fracture(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Hepatic Enzyme Increased or Abnormal Liver Function Tests(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Cognitive (Mental Processes) Decline (CD) From Baseline to the Year 2 Visit and the Final Visit(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Number of Participants With Erectile Dysfunction(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Mean Score on Euro-QoL (EQ)-5D(From Randomization at Visit 3 to Final Visit (up to 162 days))
- Mean Score on Montreal Cognitive Assessment (MoCA) Test, as an Assessment of Cognitive Function (CF)(From Randomization at Visit 3 to Final Visit (up to 162 days))