Variant AnginaPhase 4NCT03228238
ANti-Oxidant in Variant Angina (ANOVA) Trial
A Phase 4 study testing Vitamin C and Vitamin E, Statin and Standard medication for variant angina in people with Variant Angina, run by Seoul National University Hospital at 1 site in South Korea.
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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Variant Angina
- What is being tested?
- Vitamin C and Vitamin E, Statin and Standard medication for variant angina
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Sep 2014to 1 Jun 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Long-term Vitamin C+E and Statin Therapy on Vasospasm Improvement and Regression of Atheroma in Patients With Variant Angina
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)
Read the 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.
- Conditions
- Variant Angina
- Being tested
- Vitamin C and Vitamin E, Statin, Standard medication for variant angina
- Medical subject headings
- Angina Pectoris, Variant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin C and Vitamin EDrug
Also called Ascorbic acid and Tocopherol
Ascorbic acid Tablet 1g and Tocopherol Capsule 400IU
StatinDrug
Also called Atorvastatin
Atorvastatin calcium 10mg
Standard medication for variant anginaDrug
Also called Calcium Channel blocker or NG
Calcium Channel blocker or NG
| Study group | Role | What they receive |
|---|---|---|
| Dual subgroup | Experimental | 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 Receives: Drug: Vitamin C and Vitamin E; Drug: Statin; Drug: Standard medication for variant angina |
| Statin subgroup | Experimental | Standard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg Receives: Drug: Statin; Drug: Standard medication for variant angina |
| Vitamin subgroup | Experimental | Standard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU Receives: Drug: Vitamin C and Vitamin E; Drug: Standard medication for variant angina |
| Control group | Active comparator | Control subgroup : Standard medication for Variant angina only Receives: Drug: Standard medication for variant angina |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vasospasm at 6months
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Measured: at 6 months
Vasospasm at 2 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Measured: at 2 years
Vasospasm at 4 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Measured: at 4 years
Vasospasm at 6 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Measured: at 6 years
Secondary outcomes (7)
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.
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Composed improvement of Vascular endothelial function(Brachial arterial expansion capability)
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Improvement of Vascular endothelial function(Brachial arterial expansion capability)
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to baseline endothelial function test results
Measured: 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)
in Vitamin subgroup, Statin subgroup, and Dual subgroup
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Composed improvement of Arterial stiffness(Pulse wave velocity(PWV))
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Improvement of Arterial stiffness(Pulse wave velocity(PWV))
in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to baseline endothelial function test results
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Comparative analysis of improvement of Arterial stiffness(Pulse wave velocity(PWV))
in Vitamin subgroup, Statin subgroup, and Dual subgroup
Measured: at 6 months, and at 2, 4, and 6 years follow up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2017
- Study start1 Sep 2014
- Primary completion1 Jun 2024
- Study completion1 Jun 2024
Why it stopped: The study was terminated early due to slow recruitment and the Principal Investigator's retirement.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Variant AnginaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hyo-Soo Kim, Seoul National University Hospital
- Investigators
- Hyo-Soo Kim, Kim, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03228238
- Sponsor's protocol ID
- ANOVA
- Status last verified
- Apr 2026
- First submitted
- 19 Jul 2017
- Last updated
- 27 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Long-term Vitamin C+E and Statin Therapy on Vasospasm Improvement and Regression of Atheroma in Patients With Variant Angina
- ClinicalTrials.gov ID
- NCT03228238
- Acronym / sponsor ID
- ANOVA
- Conditions
- Variant Angina
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to slow recruitment and the Principal Investigator's retirement.
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Sep 2014 (actual)
- Primary completion
- 1 Jun 2024 (actual)
- Study completion
- 1 Jun 2024 (actual)
- First posted
- 24 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dual subgroup | Experimental | Drug: Vitamin C and Vitamin E, Drug: Statin, Drug: Standard medication for variant anginaStandard 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 |
| Statin subgroup | Experimental | Drug: Statin, Drug: Standard medication for variant anginaStandard medication for variant angina plus Statin Statin : Atorvastatin calcium 10mg |
| Vitamin subgroup | Experimental | Drug: Vitamin C and Vitamin E, Drug: Standard medication for variant anginaStandard medication for variant angina plus Vitamin C+E Vitamin C and Vitamin E : Ascorbic acid Tablet 1g / Tocopherol Capsule 400IU |
| Control group | Active comparator | Drug: Standard medication for variant anginaControl subgroup : Standard medication for Variant angina only |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin C and Vitamin EAlso: Ascorbic acid and TocopherolAscorbic acid Tablet 1g and Tocopherol Capsule 400IU | Drug | Dual subgroup, Vitamin subgroup |
| StatinAlso: AtorvastatinAtorvastatin calcium 10mg | Drug | Dual subgroup, Statin subgroup |
| Standard medication for variant anginaAlso: Calcium Channel blocker or NGCalcium Channel blocker or NG | Drug | Control group, Dual subgroup, Statin subgroup, Vitamin subgroup |
Primary outcome
Vasospasm at 6months
Time frame: at 6 months
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 2 years
Time frame: at 2 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 4 years
Time frame: at 4 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
Vasospasm at 6 years
Time frame: at 6 years
Severity of vasospasm in Vitamin subgroup, Statin subgroup, and Dual subgroup compared to control subgroup.
7 secondary outcomes
Changes from baseline in Vasospasm
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Composed improvement of Vascular endothelial function(Brachial arterial expansion capability)
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Improvement of Vascular endothelial function(Brachial arterial expansion capability)
Time frame: 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)
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Composed improvement of Arterial stiffness(Pulse wave velocity(PWV))
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Improvement of Arterial stiffness(Pulse wave velocity(PWV))
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Comparative analysis of improvement of Arterial stiffness(Pulse wave velocity(PWV))
Time frame: at 6 months, and at 2, 4, and 6 years follow up period
Results and safety
The study was stopped early (reason given: The study was terminated early due to slow recruitment and the Principal Investigator's retirement.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hyo-Soo Kim, Kim principal investigator
Seoul National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vitamin C and Vitamin E, Statin and Standard medication for variant angina in people with Variant Angina, run by Seoul National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated early due to slow recruitment and the Principal Investigator's retirement.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vasospasm at 6months (time frame: at 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.