Registry Based Randomized Controlled Trial of Multiple Combination Strategies of Intensive Glycemic Control to Reduce a Composite of Macrovascular and Microvascular Events in Type 2 Diabetes With Cardiovascular Risk Factors (REMATCH Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 5,950
- 试验地点
- 2
- 主要终点
- A composite of major adverse cardiovascular events (MACE) or diabetic microvascular events
研究概览
简要总结
Glycemic control is a mainstay of diabetes management to reduce the risk of microvascular complications and cardiovascular outcomes in people with type 2 diabetes (T2D). However, intensive control to near-normal glycated hemoglobin (HbA1c) yielded complex results in previous landmark trials. Potential risks of intensive glycemic control, such as hypoglycemia and weight gain, may partly contributed to the possible harms associated with this approach. Recent advances in diabetes management with development of newer antidiabetic drugs which minimize possible harms of intensive glycemic control as well as reduce cardiorenal risks enabled safer glycemic reduction. Thus, this randomized trial aims to evaluate the effects of near normalization of HbA1c with novel approaches on microvascular complications and cardiovascular outcomes in people with T2D.
详细描述
This is a multicenter, prospective, registry-based, randomized, open-label, active-comparator controlled trial involving 5,950 eligible participants with T2D, cardiovascular risk factors, and elevated HbA1c (≥7.0%). Participants will be randomly assigned to either intensive arm (targeting 6.0% of HbA1c) or standard arm (targeting 7.0% of HbA1c). The primary end point is the time to development of a composite of major adverse cardiovascular and diabetic microvascular events.
This study is designed as registry-based randomized clinical trial (RRCT), which adheres to the characteristics of both randomized clinical trial and registry-based prospective observational study. The participants will be randomly assigned into either intensive glycemic control arm or standard glycemic control arm, and the outcomes and variables will be recorded by multiple registries including hospital electronic medical records, nationwide health registry (the national health insurance service, NHIS), and Korean Statistical Information Service registry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥19 years of age
- •Patient agreed to participate in the study and signed a written informed consent form
- •Type 2 diabetes (ADA criteria)
- •HbA1c≥7.0% and <10.0% in patients receiving monotherapy, dual-combination therapy, or triple-combination therapy (when the submaximal dose was administered) with oral antidiabetic drugs (OADs)
- •Any of the following:
- •A. Patients who one or more of the following conditions
- •Coronary artery disease
- •Atherosclerotic ischemic stroke, transient ischemic attack, carotid artery disease, peripheral artery disease, abdominal aortic aneurysm
- •Prevalence of diabetes ≥10 years
- •Left ventricular hypertrophy
- •Albuminuria
- •Chronic kidney disease (eGFR<60mL/min/1.73m²)
- •Diabetic Retinopathy
- •Diabetic neuropathy or B. Patients who have two or more of the following cardiovascular risk factors
- •(1) Family history of early-onset ASCVD (first-degree relatives with disease before age 55 for men and before age 65 for women) (2) Hypertension (on medication or with SBP≥140 mm Hg or DBP≥90 mm Hg) (3) Low HDL cholesterol concentration (<40 mg/dL) (4) Current smoker (5) Obese (BMI≥25 kg/m²)
排除标准
- •Type 1 diabetes
- •Estimated GFR<45 ml/min/1.73m²
- •AST or ALT greater than 3 times the normal upper limit
- •Symptomatic heart failure (NYHA Class III or IV)
- •History of hospitalization for acute cardiovascular events within 3 months prior to the date of consent
- •Currently in active treatment for malignancy
- •Contraindications for each assigned drug, as applicable
- •Pregnant and nursing women
- •If the investigator determines that assignment to the standard glycemic control arm raises ethical concerns
研究组 & 干预措施
Standard treatment arm (HbA1c 7.0% target)
Metformin/DPP-4i-based or Metformin/SGLT2i-based dual-combination therapy. Treatment and Follow-up : Maximum 4 years
干预措施: Dual-combination therapy (Drug)
Intensive treatment arm (HbA1c 6.0% target): plus real-time CGM
Randomly assigned into 2 sub-groups Device: Dexcom G7 plus Kakaohealthcare Pasta. (Barozen Fit is also available.) Treatment and Follow-up : Maximum 4 years
干预措施: Triple-combination therapy (Drug)
Intensive treatment arm (HbA1c 6.0% target): plus real-time CGM
Randomly assigned into 2 sub-groups Device: Dexcom G7 plus Kakaohealthcare Pasta. (Barozen Fit is also available.) Treatment and Follow-up : Maximum 4 years
干预措施: Dexcom G7, Pasta (Device)
结局指标
主要结局
A composite of major adverse cardiovascular events (MACE) or diabetic microvascular events
时间窗: 6-month, 1-, 2-, 3-, 4-year after enrollment
The time from the date of randomization to the first occurrence of any of the events or records in A\*\* and B\*\* as defined below. \[\*\*A.Major adverse cardiovascular events (MACEs): (1) Death from cardiovascular causes (2) Non-fatal stroke (3) Non-fatal myocardial infarction (4) Hospitalization due to unstable angina (5) Hospitalization due to heart failure (6) Hospitalization due to peripheral artery disease (7) Coronary or peripheral revascularization \*\*B.Diabetic microvascular events * B1. A composite of kidney events: 1. Death from kidney causes 2. Development of end-stage renal disease 3. Sustained decline in eGFR of 40% or more from baseline 4. Occurrence of marked albuminuria, * B2. A composite of eye events: 1. Development or progression of diabetic retinopathy (proliferative diabetic retinopathy or macular edema) 2. Blindness due to diabetic retinopathy 3. Surgical treatment of diabetic retinopathy or intravitreal injections\]
次要结局
- Composite endpoint of cardiorenal events_#1(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Composite endpoint of cardiorenal events_#2(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Level of HbA1c (glycated haemoglobin)(6-month, 1-, 2-, 3-, 4-year after enrollment)
- The proportion of participants who exhibited a weight change (either gain or loss) of 10% or more(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Change in waist circumference at each time point from baseline(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Change in estimated glomerular filtration rate (eGFR) from baseline(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Change in lipid panel(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Change in urine albumin to creatinine ratio (UACR) from baseline(6-month, 1-, 2-, 3-, 4-year after enrollment)
- Safety endopoints(6-month, 1-, 2-, 3-, 4-year after enrollment)
研究者
Kyu Chang Won
Professor
Yeungnam University Hospital