ANti-Oxidant in Variant Angina (ANOVA) Trial

Variant Angina Clinical 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03228238
• Other study ID #: ANOVA
• Status: Recruiting
• Phase: Phase 4
• First received: July 19, 2017
• Last updated: July 20, 2017
• Start date: September 1, 2014
• Est. completion date: February 28, 2021

Study information

• Verified date: July 2017
• Source: Seoul National University Hospital
• Contact: Hyo-Soo Kim, MD, PhD
• Phone: 82-2-2072-2226
• Email: hyosoo[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 28, 2021
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Angina Pectoris
• Angina Pectoris, Variant
• Variant Angina

Intervention

Drug:
• Vitamin C and Vitamin E
Ascorbic acid Tablet 1g and Tocopherol Capsule 400IU
• Statin
Atorvastatin calcium 10mg
• Standard medication for variant angina
Calcium Channel blocker or NG

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

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