Clinical trial NCT03228238: ANti-Oxidant in Variant Angina (ANOVA) Trial
Official title: Effects of Long-term Vitamin C+E and Statin Therapy on Vasospasm Improvement and Regression of Atheroma in Patients With Variant Angina
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Variant Angina
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2017-07-24
Enrollment: 300
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose Objectives

1. To evaluate the anti-oxidant effect of long-term Vitamin C+E therapy on coronary vasospasm improvement.
2. To evaluate the anti-oxidant effect of long-term statin therapy on coronary vasospasm improvement.
3. To evaluate the effect of long-term Vitamin C+E and statin therapy on regression of atheroma in target coronary vessels via intravascular ultrasound.
4. 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.
5. 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)

Detailed description: 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)

1. 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.
2. 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.
3. 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

1. Control subgroup : Standard medication for Variant angina only
2. Vitamin subgroup : Standard medication + Vitamin C+E
3. Statin subgroup : Standard medication + Statin
4. Dual subgroup : Standard medication + Vitamin C+E + Statin

Patients in Negative group will be prescribed only for standard medication for variant angina.

Patient Enrollment: Recruiting 300 patients(100 patients for each group, as 25 patients for each subgroups) from September 2014 through February 2021 at single center in Korea(Seoul National University Hospital)

Patient Follow-Up: Clinical follow-up will occur at 1, and 6 months, and at 2, 4, and 6 years. Investigator or designee may conduct follow-up as telephone contacts or office visits.

Eligibility criteria: Inclusion Criteria:

1. Subject must be at least 30 years of age.
2. 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.
3. Subject must have symptoms that are consistent with vasospastic angina with planned Coronary angiography and Provocation test.

Exclusion Criteria:

1. Patient who has organic coronary stenosis in main coronary branch at least 50% luminal narrowing after intracoronary nitroglycerin injection
2. Patient who has continuously taken Vitamin C or Vitamin E or Statin within 3months before Admission
3. Creatinine level ≥ 2.0mg/dL or dependence on dialysis.
4. Severe hepatic dysfunction (AST and ALT: 3 times upper normal reference values).
5. Active Myopathy or elevated Creatine kinase enzyme level (3 times upper normal reference values).
6. History of Severe hepatic dysfunction or Rhabdomyolysis due to statin side effect
7. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
8. History of Urolithiasis
9. 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).

Primary outcomes:
measure: Vasospasm at 6months
timeFrame: at 6 months
measure: Vasospasm at 2 years
timeFrame: at 2 years
measure: Vasospasm at 4 years
timeFrame: at 4 years
measure: Vasospasm at 6 years
timeFrame: at 6 years
Secondary outcomes:
measure: Changes from baseline in Vasospasm
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Composed improvement of Vascular endothelial function(Brachial arterial expansion capability)
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Improvement of Vascular endothelial function(Brachial arterial expansion capability)
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Comparative analysis of improvement of Vascular endothelial function(Brachial arterial expansion capability)
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Composed improvement of Arterial stiffness(Pulse wave velocity(PWV))
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Improvement of Arterial stiffness(Pulse wave velocity(PWV))
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
measure: Comparative analysis of improvement of Arterial stiffness(Pulse wave velocity(PWV))
timeFrame: at 6 months, and at 2, 4, and 6 years follow up period
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Hyo-Soo Kim, Kim
role: PRINCIPAL_INVESTIGATOR
References: