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
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 1,332
- 试验地点
- 1
- 主要终点
- Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •50% stenosis on any imaging of coronary, carotid or lower extremity arteries
- •ankle/brachial index <0.9 OR
- •Age ≥ 60 years and at least 2 of the following cardiovascular disease risk factors:
- •current tobacco use
- •LDL-c ≥3.4 mmol/L (130 mg/dL) or on a lipid lowering medication
- •HDL-c < 1.0 mmol/L (40 mg/dL) for men and < 1.3 mmol/L (50 mg/dL) for women or triglycerides ≥ 2.3 mmol/L (200 mg/dL)
- •BP lowering medication use or untreated SBP ≥ 140 mmHg or DBP ≥ 95 mmHg
- •Waist to hip ratio > 1.0 for men and > 0.8 for women
- •On no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the MOP) with stable dosing for 10 weeks prior to screening
排除标准
- •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
- •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 (other than prophylactic)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 2.5 times the upper limit of normal
- •A prior heart transplant or awaiting a heart transplant
- •Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin D therapy
- •Regular use of or indication for greater than 400IU of vitamin D daily
- •Clinically or medically unstable with expected survival < 1 year
- •Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data
- •Any other factor likely to limit protocol compliance or reporting of adverse events
- •Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator
- •Contraindications to or history of hypersensitivity to the investigational products
- •History of renal stones within the past 2 years
- •Participation in another clinical trial of an investigational agent
研究组 & 干预措施
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.
干预措施: pioglitazone (Drug)
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.
干预措施: rosiglitazone (Drug)
TZD placebo
Matching placebo tablet was administered once a day (OD) for the duration of 5.5 years
干预措施: Placebo (Dietary Supplement)
Vitamin D
Active comparator
干预措施: Vitamin D (Dietary Supplement)
Vitamin D placebo
Placebo Comparator
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Number of Participants With the Indicated Components of the Composite Cardiovascular Outcome for Thiazolidinedione (TZD)
时间窗: 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
时间窗: 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.
次要结局
- 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))