Effects of Long-term Vitamin C+E and Statin Therapy on Vasospasm Improvement and Regression of Atheroma in Patients With Variant Angina
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 320
- 试验地点
- 2
- 主要终点
- Vasospasm at 6 years
研究概览
简要总结
Purpose Objectives
- To evaluate the anti-oxidant effect of long-term Vitamin C+E therapy on coronary vasospasm improvement.
- To evaluate the anti-oxidant effect of long-term statin therapy on coronary vasospasm improvement.
- To evaluate the effect of long-term Vitamin C+E and statin therapy on regression of atheroma in target coronary vessels via intravascular ultrasound.
- To find out the role of vascular endothelium in variant angina via evaluating long-term Vitamin C+E and statin therapy on improvement in vascular endothelial function by assessing brachial arterial expansion capability.
- To find out the role of vascular endothelium in variant angina via evaluating long-term Vitamin C+E and statin therapy on improvement in arterial stiffness by assessing pulse wave velocity(PWV)
详细描述
Study Design: Prospective, open label, Four-arm, randomized single-center trial to test the effect long-term Vitamin C+E and Statin therapy on vasospasm improvement and regression of atheroma in patients with variant angina.
After provocation test, patients will be classified into three groups.(See below)
- Negative group : Patients who have symptoms that are consistent with vasospastic angina but only show luminal narrowing less than 50% on coronary angiography during provocation test.
- Mild Spastic group : Patients who have symptoms that are consistent with vasospastic angina and show luminal narrowing over 50% to less than 90% on coronary angiography during provocation test.
- Severe Spastic group : Patients who have symptoms that are consistent with vasospastic angina and show luminal narrowing over 90% on coronary angiography during provocation test.
In each group (except for patient in Negative group), patients will be randomized in a two by two factorial manner according to the study drug therapy (Vitamin C+E vs. no Vitamin C+E) (Statin vs. no Statin) As a result, patients in each group(except for patient in Negative group) will be randomized to 4 treatment subgroups, which are
- Control subgroup : Standard medication for Variant angina only
- Vitamin subgroup : Standard medication + Vitamin C+E
- Statin subgroup : Standard medication + Statin
- Dual subgroup : Standard medication + Vitamin C+E + Statin
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
- None
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be at least 30 years of age.
- •Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Vitamin C+E or Statin or Dual, and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.
- •Subject must have symptoms that are consistent with vasospastic angina with planned Coronary angiography and Provocation test.
排除标准
- •Patient who has organic coronary stenosis in main coronary branch at least 50% luminal narrowing after intracoronary nitroglycerin injection
- •Patient who has continuously taken Vitamin C or Vitamin E or Statin within 3months before Admission
- •Creatinine level ≥ 2.0mg/dL or dependence on dialysis.
- •Severe hepatic dysfunction (AST and ALT: 3 times upper normal reference values).
- •Active Myopathy or elevated Creatine kinase enzyme level (3 times upper normal reference values).
- •History of Severe hepatic dysfunction or Rhabdomyolysis due to statin side effect
- •Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
- •History of Urolithiasis
- •Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
研究组 & 干预措施
Dual subgroup
Standard medication for variant angina plus Vitamin C+E plus Statin Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU Statin : Atorvastatin calcium 10mg
干预措施: Vitamin C and Vitamin E (Drug)
Statin subgroup
Standard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg
干预措施: Statin (Drug)
Statin subgroup
Standard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg
干预措施: Standard medication for variant angina (Drug)
Vitamin subgroup
Standard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU
干预措施: Vitamin C and Vitamin E (Drug)
Dual subgroup
Standard medication for variant angina plus Vitamin C+E plus Statin Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU Statin : Atorvastatin calcium 10mg
干预措施: Statin (Drug)
Vitamin subgroup
Standard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU
干预措施: Standard medication for variant angina (Drug)
Dual subgroup
Standard medication for variant angina plus Vitamin C+E plus Statin Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU Statin : Atorvastatin calcium 10mg
干预措施: Standard medication for variant angina (Drug)
Control group
Control subgroup : Standard medication for Variant angina only
干预措施: Standard medication for variant angina (Drug)
结局指标
主要结局
Vasospasm at 6 years
时间窗: at 6 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 2 years
时间窗: at 2 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 6months
时间窗: at 6 months
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 4 years
时间窗: at 4 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
次要结局
- Composed improvement of Arterial stiffness(Pulse wave velocity(PWV))(at 6 months, and at 2, 4, and 6 years follow up period)
- Comparative analysis of improvement of Arterial stiffness(Pulse wave velocity(PWV))(at 6 months, and at 2, 4, and 6 years follow up period)
- Improvement of Vascular endothelial function(Brachial arterial expansion capability)(at 6 months, and at 2, 4, and 6 years follow up period)
- Composed improvement of Vascular endothelial function(Brachial arterial expansion capability)(at 6 months, and at 2, 4, and 6 years follow up period)
- Changes from baseline in Vasospasm(at 6 months, and at 2, 4, and 6 years follow up period)
- Comparative analysis of improvement of Vascular endothelial function(Brachial arterial expansion capability)(at 6 months, and at 2, 4, and 6 years follow up period)
- Improvement of Arterial stiffness(Pulse wave velocity(PWV))(at 6 months, and at 2, 4, and 6 years follow up period)
研究者
Hyo-Soo Kim
Director of Cardiac Catheterization Laboratory & Coronary Intervention
Seoul National University Hospital