ANti-Oxidant in Variant Angina (ANOVA) Trial

Sponsor

Seoul National University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03228238

Collaborator

(none)

300

Enrollment

Location

Arms

77.9

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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)

Condition or Disease	Intervention/Treatment	Phase
Variant Angina	Drug: Vitamin C and Vitamin E Drug: Statin Drug: Standard medication for variant angina	Phase 4

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)

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of Long-term Vitamin C+E and Statin Therapy on Vasospasm Improvement and Regression of Atheroma in Patients With Variant Angina

Actual Study Start Date :

Sep 1, 2014

Anticipated Primary Completion Date :

Sep 1, 2020

Anticipated Study Completion Date :

Feb 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Vitamin C and Vitamin E Ascorbic acid Tablet 1g and Tocopherol Capsule 400IU Other Names: Ascorbic acid and Tocopherol Drug: Statin Atorvastatin calcium 10mg Other Names: Atorvastatin Drug: Standard medication for variant angina Calcium Channel blocker or NG Other Names: Calcium Channel blocker or NG
Experimental: Statin subgroup Standard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg	Drug: Statin Atorvastatin calcium 10mg Other Names: Atorvastatin Drug: Standard medication for variant angina Calcium Channel blocker or NG Other Names: Calcium Channel blocker or NG
Experimental: Vitamin subgroup Standard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU	Drug: Vitamin C and Vitamin E Ascorbic acid Tablet 1g and Tocopherol Capsule 400IU Other Names: Ascorbic acid and Tocopherol Drug: Standard medication for variant angina Calcium Channel blocker or NG Other Names: Calcium Channel blocker or NG
Active Comparator: Control group Control subgroup : Standard medication for Variant angina only	Drug: Standard medication for variant angina Calcium Channel blocker or NG Other Names: Calcium Channel blocker or NG

Outcome Measures

Primary Outcome Measures

Vasospasm at 6months [at 6 months]
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 2 years [at 2 years]
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 4 years [at 4 years]
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 6 years [at 6 years]
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.

Secondary Outcome Measures

Changes from baseline in Vasospasm [at 6 months, and at 2, 4, and 6 years follow up period]
Changes of Vasospasm in Control subgroup, Vitamin subgroup, Statin subgroup, and Dual subgroup compared to baseline vasospasm assessed by provocation test.
Composed improvement of Vascular endothelial function(Brachial arterial expansion capability) [at 6 months, and at 2, 4, and 6 years follow up period]
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup
Improvement of Vascular endothelial function(Brachial arterial expansion capability) [at 6 months, and at 2, 4, and 6 years follow up period]
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to baseline endothelial function test results
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]
in Vitamin subgroup, Statin subgroup, and Dual subgroup
Composed improvement of Arterial stiffness(Pulse wave velocity(PWV)) [at 6 months, and at 2, 4, and 6 years follow up period]
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup
Improvement of Arterial stiffness(Pulse wave velocity(PWV)) [at 6 months, and at 2, 4, and 6 years follow up period]
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to baseline endothelial function test results
Comparative analysis of improvement of Arterial stiffness(Pulse wave velocity(PWV)) [at 6 months, and at 2, 4, and 6 years follow up period]
in Vitamin subgroup, Statin subgroup, and Dual subgroup

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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).