Prospective Double-Blinded Randomized Placebo-controlled Multicenter Study Evaluating the Impact of Dietary Supplement "Tertinat" on Major Adverse Cardiovascular Events in ATherosclerotic Patients After Coronary Revascularization Surgery.
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,228
- 试验地点
- 11
- 主要终点
- Frequency of fatal cardiovascular events
研究概览
简要总结
The aim of this double-blind, randomized, placebo-controlled, multicenter study is to evaluate the pathogenetic effects of the dietary supplement "Tertinat" on a fundamental mechanism of atherosclerosis development: its ability to inhibit pathological desialylation of low-density lipoproteins (LDL). According to the protocol's scientific hypothesis, the loss of sialic acid from the surface of LDL converts them into highly atherogenic particles, which are actively captured by vascular macrophages, triggering the formation of unstable atherosclerotic plaques. Over 24 months of daily administration of 330 mg of epigallocatechin-3-gallate, along with standard therapy, will evaluate not only the incidence of major cardiovascular events (MACE) in atherosclerotic patients who have undergone the procedure of surgical revascularization, but also the direct dynamics of recovery of sialic acid levels in LDL particles in patients' blood. The study aims to confirm that preventing LDL desialylation reduces overall serum atherogenicity, prevents cholesterol accumulation within macrophages in vivo, and thereby provides a proven clinical effect - a reduced risk of myocardial infarction, stroke, unstable angina, heart failure, and the need for repeated revascularization in patients after coronary artery bypass grafting or stenting.
详细描述
- Rationale
Dietary supplement "Tertinat" is based on green tea extract with a standardized content of epigallocatechin-3-gallate. According to in-silico and in vitro data, epigallocatechin-3-gallate is an inhibitor of neuraminidases, thus capable of preventing desialylation of low-density lipoprotein (LDL). In pilot study it has been demonstrated that peroral intake of Tertinat leads to a sustained increase in the level of LDL sialic acid content in the blood of study participants in vivo, as well as a decrease in the serum-induced intracellular cholesterol accumulation by macrophages in vitro.
The available published data demonstrate the anti-inflammatory effects of epigallocatechin-3-gallate and its ability to regulate lipid metabolism, which potentially indicate to the multiplicity of mechanisms of its anti-atherogenic action. 2. Study Objectives
The objective of the study is to evaluate the effect of long-term intake of dietary supplement Tertinat on the rate of major adverse cardiovascular events (MACE). 3. Study Hypothesis
Oral administration of Tertinat in addition to the main therapy reduces the rate of cardiovascular events in patients with coronary atherosclerosis via restoring LDL sialic acid content and lowering serum atherogenicity. 4. Primary Endpoints:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
A randomized, double-blinded, placebo-controlled trial
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged 45-75
- •Patients with atherosclerotic cardiovascular diseases who have passed revascularization procedure within last 3 months prior to the inclusion in the study
- •Atherosclerotic cardiovascular diseases may include coronary heart disease, and/or coronary atherosclerosis, and/or atherosclerosis of brachiocephalic / limb / renal arteries.
- •Patients who have undergone instrumental and laboratory examinations (ECG, ultrasound / CT / angiography, biochemical tests - total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, blood glucose, C-reactive protein), and the data from above examinations from medical records are available.
- •The principal patient's abitity for follow-up questioning and examination at 12 and 24 months apart from inclusion in the study.
- •The signed informed consent.
排除标准
- •Critical and urgent cardiovascular conditions: tissue ischemia stage III-IV, stroke, acute coronary syndrome, acute myocardial infarction, chronic heart failure III and IV class NYHA (New York Heart Association).
- •Other critical and urgent conditions not associated with cardiovascular diseases, including the need for urgent interventions, chronic renal failure stages IV-V (creatinine clearance < 30 ml / min according to the Cockcroft-Gault Equation)
- •Systemic autoimmune diseases in medical history, including: rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, autoimmune vasculitis, ulcerative colitis.
- •Significant weight loss (> 10% of body weight in the previous year) of unknown etiology.
- •Conditions that limit adherence to participation in the study (dementia, neuropsychiatric diseases, drug addiction, alcoholism, etc.).
- •Participation in other clinical studies (or use of investigational substances) within 3 months prior to study entry.
- •Carriers of HIV or viral hepatitis
- •Pregnancy or breast feeding
- •Refusal to participate in the study / to sigh informed concent.
研究组 & 干预措施
Tertinat
干预措施: Tertinat (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency of fatal cardiovascular events
时间窗: Evaluated in 12 months from revascularization interventions
Fatal cardiovascular events include: death from myocardial infarction, other forms of coronary heart disease (CHD), stroke, including sudden death and death within 24 hours of symptom onset, death from other non-coronary cardiovascular diseases except definitely non-atherosclerotic causes of death.
Frequency of clinically significant cardiovascular events
时间窗: Evaluated in 12 months from revascularization interventions
Clinically significant cardiovascular events include: acute myocardial infarction and acute coronary syndrome, acute cerebrovascular accident, progressive heart failure, hospitalization due to critical limb ischemia.
The rate of fatal cardiovascular events
时间窗: Evaluated in 12 and 24 months from revascularization interventions
\- Cardiovascular death (death from myocardial infarction, other forms of coronary heart disease; death from stroke) The deaths from other non-coronary cardiovascular diseases and from definitively non-atherosclerotic causes of death are registered but not considered as primary endpoints.
The rate of non-fatal cardiovascular events
时间窗: Evaluated in 12 and 24 months from revascularization interventions
* Non-fatal myocardium infarction * Non-fatal stroke / transient ischemic attack * Unstable angina / Acute coronary syndrome * Heart failure / Hospitalization due to critical ischemia
The rate of repeated revascularization procedures
时间窗: Evaluated in 12 and 24 months from revascularization interventions
* Percutaneous Endovascular Interventions (PEI): Angioplasty (PTCA); Stenting; Atherectomy * Surgical Revascularization: Coronary Artery Bypass Grafting (CABG); Peripheral Artery Bypass; Endarterectomy * Medical \& Emerging Revascularization: Thrombolytic Therapy ("Clot Busters")
次要结局
- Change in the severity of stenosis of the affected due to the underlying disease and/or carotid and femoral arteries according to ultrasound examination(Evaluated in 12 months)
- Atherogenicity changes in serum blood(Evaluated in 12 months)
- Changes in LDL sialic acid levels(Evaluated in 12 months)
- Changes in lipid profile indicators (total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol - calculated value)(Evaluated in 12 months)
- Changes in circulating immune complex cholesterol levels(Evaluated in 12 months)
- The change in LDL sialic acid content(Evaluated in 12 and 24 months from revascularization interventions)
- The change in blood serum-induced intracellular cholesterol accumulation (serum atherogenicity)(Evaluated in 12 and 24 months from revascularization interventions)
- The change in total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol(Evaluated in 12 and 24 months from revascularization interventions)
- The change in the cholesterol level of circulating immune complexes(Evaluated in 12 and 24 months from revascularization interventions)
- The change in the extent of stenosis of the affected coronary, carotid and femoral arteries(Evaluated in 12 and 24 months from revascularization interventions)