Effect of Pioglitazone on Insulin Resistance, Progression of Atherosclerosis and Clinical Course of Coronary Heart Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Сardiovascular Death
研究概览
简要总结
Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues.
Our aim will to study the effect of pioglitazone on insulin resistance, the clinical course of atherosclerosis and coronary heart disease (CHD).
The study will include 43 patients with coronary artery disease. Patients will be divided into the study group - 20 patients, in whom pioglitazone will be included in the combined therapy at a dose of 15 mg 1 time per day in the morning, and the control group - 23 patients receiving standard complex drug therapy over 6 months. Patients will be underwent clinical examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism.
The end primary points of the study will be the onset of death due to myocardial infarction, coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or unstable angina (UA).
Predefined secondary end points included carotic atherosclerotic leisure (carotic intima-media thickness, diameter of stenosis, presents of atherosclerotic plaque), systemic inflammation level (the level of C reactive protein), lipid metabolism (levels of serum total cholesterol, triglycerides, high and low density lipoproteins), level of insulin resistance ( oral glucose tolerance test, blood glucose).
详细描述
The study will include 43 people aged between 45 and 68 who suffered from ischemic heart disease. Before starting the study, all participants will give written informed consent, will be obtained of the Commission on Bioethics at Ukrainian Medical Stomatological Academy. Inclusion criteria will be as follows: stable exertional angina, type 2 diabetes mellitus (DM) without receiving injectable antidiabetic drugs. Exclusion criteria will be: the presence of myocardial infarction history, intervention, malignant arterial hypertension (AH), chronic heart failure (HF) of III-IV functional class (FC), systemic connective tissue diseases, cancer and oncohematological diseases, severe infectious diseases, chronic inflammatory diseases, history of acute cerebrovascular accidents, disorders of cardiac rhythm by atrial fibrillation type. The end study will be the primary points: the onset of death due to myocardial infarction, coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or unstable angina (UA).
The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory insufficiency according to the classification of New York Heart Association (NYHA). Bicycle ergometry will perform on "Veloergotest 05" (Ukraine) via step increasing loading capacity with a consequent increase under control of electrocardiogram (ECG) and BP. The force of step I will be 150 kgm / min (25 W); II - 300 kgm / min (50 W); III - 450 kgm / min (75 W); IV - 600 kgm / min (100 W); V - 750 kgm / min (125 W); VI - 900 kgm / min (150 W), the duration of each step was 3 minutes. Tolerance of CHD patients to exercise will calculate from the value of the threshold load capacity and volume of work performed. The threshold load capacity of 150 kgm / min (25 W) was considered very low and consistent with angina FC IV; 300 kgm / min (50 W) - low, FC III; 450-600 kgm / min (75-100 W) - average, FC II; 750 kgm / min (125 W) and above - high exercise capacity, FC I. The criteria will cease bicycle ergometry termination conventional clinical or ECG signs of myocardial ischemia.
Prior to inclusion in the clinical trial, all patients will receive conventional treatment and will screening examination to verify the diagnosis of coronary heart disease and type 2 diabetes.
After screening, we will selected 43 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also will receive recommendations on diet and lifestyle changes. Patients will receive the conventional treatment for at least one month to achieve stable parameters.
On the first day of the study, blood samples will take from all patients, clinical examination was conducted. After clinical and laboratory studies, patients will randomized by gender, age and severity of clinical manifestations of coronary heart disease. As a result of randomization, patients will divide into the study group (n = 20) and control group (n = 23). The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the morning ("Pioglar", Ranbaxy, India) for 6 months. Patients of the control group will continue to receive only a standard set of drug therapy. Re-examination will carry out in 6 months.
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
- 45 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •stable exertional angina,
- •type 2 diabetes mellitus (DM) without receiving injectable antidiabetic drugs
排除标准
- •the presence of myocardial infarction history, intervention;
- •malignant arterial hypertension (AH);
- •chronic heart failure (HF) of III-IV functional class (FC);
- •systemic connective tissue diseases;
- •cancer and oncohematological diseases, severe infectious diseases, chronic inflammatory diseases;
- •history of acute cerebrovascular accidents;
- •disorders of cardiac rhythm by atrial fibrillation type.
研究组 & 干预措施
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Pioglitazone 15 mg Tablet (Drug)
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Isosorbide Dinitrate 10Mg Tablet (Drug)
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Acetylsalicylic Acid 75Mg Tablet (Drug)
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Bisoprolol Fumarate 2.5 MG Oral Tablet (Drug)
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Rosuvastatin Calcium 20 MG Oral Tablet (Drug)
Pioglitazone + Standard Care
20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
干预措施: Ramipril 5 MG (Drug)
Standard Care
23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
干预措施: Isosorbide Dinitrate 10Mg Tablet (Drug)
Standard Care
23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
干预措施: Acetylsalicylic Acid 75Mg Tablet (Drug)
Standard Care
23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
干预措施: Bisoprolol Fumarate 2.5 MG Oral Tablet (Drug)
Standard Care
23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
干预措施: Rosuvastatin Calcium 20 MG Oral Tablet (Drug)
Standard Care
23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
干预措施: Ramipril 5 MG (Drug)
结局指标
主要结局
Сardiovascular Death
时间窗: Baseline and 1 year
Number of Participants with cardiovascular death
Coronary Artery Bypass [Coronary Revascularization]
时间窗: Baseline and 1 year
Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)
Percutaneous Coronary Intervention [Coronary Revascularization]
时间窗: Baseline and 1 year
Number of Participants with incidence of percutaneous coronary intervention.
Safety and Tolerability 1
时间窗: Baseline, 6 month and 1 year
Liver injury: mean values of ALT
Cardiovascular Hospitalization
时间窗: Baseline and 1 year
Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)
Safety and Tolerability 2
时间窗: Baseline, 6 month and 1 year
Liver injury: mean levels of total bilirubin
Safety and Tolerability 4
时间窗: Baseline and 1 year
Kidneys injury: mean values of creatinine
Safety and Tolerability 3
时间窗: Baseline and 1 year
Kidney injury: mean values of the microalbuminuria
次要结局
- Diameter of Stenosis [Carotic Atherosclerotic Lesions](Baseline and 1 year)
- Thickness of the Intima-media Complex(Baseline, 6 month and 1 year)
- Carotic Atherosclerotic Lesions(Baseline and 1 year)
- Lipid Metabolism 2(Baseline, 6 month and 1 year)
- Systemic Inflammation Level(Baseline and 1 year)
- Lipid Metabolism 1(Baseline, 6 month and 1 year)
- Lipid Metabolism 3(Baseline and 1 year)
研究者
Igor Kaydashev
Head of Internal Medicine Department #3
Ukrainian Medical Stomatological Academy