ANti-Oxidant in Variant Angina (ANOVA) Trial

Seoul National University

Status and phase: Unknown; Phase 4

Conditions: Variant Angina

Treatments: Drug: Statin; Drug: Vitamin C and Vitamin E; Drug: Standard medication for variant angina

Study type: Interventional

Funder types: Other

Identifiers

NCT03228238

ANOVA

Details and patient eligibility

About

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)

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 4 patient groups

Dual subgroup

Experimental group

Description:

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

Treatment:

Drug: Standard medication for variant angina

Drug: Vitamin C and Vitamin E

Drug: Statin

Statin subgroup

Experimental group

Description:

Standard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg

Treatment:

Drug: Standard medication for variant angina

Drug: Statin

Vitamin subgroup

Experimental group

Description:

Standard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU

Treatment:

Drug: Standard medication for variant angina

Drug: Vitamin C and Vitamin E

Control group

Active Comparator group

Description:

Control subgroup : Standard medication for Variant angina only

Treatment:

Drug: Standard medication for variant angina