AzTrials
AzTrials

Patent Foramen OvalePhase 2COMPETENCT05546320

Comparison of the Effect of Medication Therapy in Alleviating Migraine With Patent Foramen Ovale

A Phase 2 study testing Aspirin 300mg, Metoprolol 25mg and Clopidogrel 75mg in people with Patent Foramen Ovale and Migraine, run by Chinese Academy of Medical Sciences, Fuwai Hospital at 39 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Migraine attack is an episodic disorder that affects approximately 12% of the population. Previous studies have shown that 41-48% of migraineur have a combination of patent foramen ovale (PFO). Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Patent Foramen Ovale, Migraine
What is being tested?
Aspirin 300mg, Metoprolol 25mg and Clopidogrel 75mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,000 participants
Where
39 sitesChina
Study dates
15 Oct 2022to 26 Mar 2025
Phase
Phase 2
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 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Participants must meet all of the following criteria:
  • Aged 18 to 64 years at Visit 1.
  • Diagnosis of migraine with or without aura confirmed by a neurologist, according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.
  • History of migraine for more than 1 year, with an average of at least 4 migraine days per month during the 12-week screening period, as recorded in a headache diary and confirmed by the investigator at Visit 2.
  • Patent foramen ovale (PFO) diagnosed by transcranial Doppler (TCD), transthoracic echocardiography (TTE), or transesophageal echocardiography (TEE), with a right-to-left shunt at the atrial level.
  • Provision of written informed consent and willingness to comply with follow-up procedures.

Who cannot join

  • Participants will be excluded if any of the following apply:
  • Secondary headache attributable to other causes.
  • History of transient ischemic attack, stroke, or intracranial hemorrhage.
  • History of pacemaker implantation, atrial septal defect closure, or left atrial appendage closure.
  • Right-to-left intracardiac shunt due to causes other than PFO.
  • Contraindications to antiplatelet or anticoagulant therapy, including thrombocytopenia, major trauma, active bleeding, decompensated cirrhosis, or drug allergy.
Show all 15Show fewer
  • Contraindications to beta-blocker therapy, including hypotension, severe bradycardia, atrioventricular block, asthma, or drug allergy.
  • Poorly controlled atrial fibrillation at Visit 1.
  • Poorly controlled hypertension at Visit 1, defined as blood pressure >160/90 mmHg despite regular medication.
  • Inability to maintain a headache diary or to reliably report headache symptoms.
  • Use of anticoagulants (e.g., warfarin, rivaroxaban) or antiplatelet agents (e.g., aspirin, clopidogrel, ticagrelor) within 12 weeks prior to Visit 2.
  • Use of metoprolol within 12 weeks prior to Visit 2.
  • Pregnancy, intention to become pregnant during the study period, or planned elective surgery during the study period.
  • Any condition that, in the investigator's opinion, may pose significant risk, confound study results, or interfere with participation.
  • Any other reasons (e.g., likely non-adherence, inability to attend follow-up visits, or planned relocation) that render the participant unsuitable for the study in the investigator's judgment.

Trial locations and contacts

39 sites in 1 country.

39 sites in 1 country

China39 sites

  • Beijing Tiantan Hospital, Capital Medical University

    Beijing, Beijing Municipality

  • National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences

    Beijing, Beijing Municipality

  • Clinical Medical College and Affiliated Hospital of Chengdu University

    Chengdu, Sichuan

  • The First Affiliated Hospital of Chengdu Medical College

    Chengdu, Sichuan

  • West China Hospital of Sichuan University

    Chengdu, Sichuan

  • Dalian Municipal Central Hospital

    Dalian, Liaoning

  • Dalian University Affiliated Zhongshan Hospital

    Dalian, Liaoning

  • Daqing Longnan Hospital

    Daqing, Heilongjiang

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong

  • Guizhou Provincial People's Hospital

    Guiyang, Guizhou

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, Anhui

  • The First Affiliated Hospital of USTC

    Hefei, Anhui

  • The Second Hospital, Cheeloo College of Medicine, Shandong University

    Jinan, Shandong

  • Fuwai Cardiovascular Hospital of Yunnan Province

    Kunming, Yunnan

  • The First Affiliated Hospital of Kunming Medical University

    Kunming, Yunnan

  • Gansu Provincial Hospital

    Lanzhou, Gansu

  • The Second Affiliated Hospital of Lanzhou University

    Lanzhou, Gansu

  • Jiangxi Provincial People's Hospital Affiliated to Nanchang University

    Nanchang, Jiangxi

  • The Second Affiliated Hospital of Nanchang University

    Nanchang, Jiangxi

  • The First Affiliated Hospital, Guangxi Medical University

    Nanning, Guangxi

  • Nanyang Central Hospital

    Nanyang, Henan

  • Qingdao Fuwai Cardiovascular Hospital

    Qingdao, Shandong

  • Shangqiu First People's Hospital

    Shangqiu, Henan

  • The Fourth People's Hospital of Shenyang

    Shenyang, Liaoning

  • Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen Hospital

    Shenzhen, Guangdong

  • The Seventh Affiliated Hospital of Sun Yat-sen University

    Shenzhen, Guangdong

  • Hebei General Hospital

    Shijiazhuang, Hebei

  • The Second Hospital of Hebei Medical University

    Shijiazhuang, Hebei

  • Suzhou Hospital of Anhui Medical University

    Suzhou, Anhui

  • First Hospital of Shanxi Medical University

    Taiyuan, Shanxi

  • The Second Affiliated Hospital of Xinjiang Medical University

    Ürümqi, Xinjiang

  • Wuhan Asia Heart Hospital

    Wuhan, Hubei

  • Xiangyang Central Hospital

    Xiangyang, Hubei

  • Xingtai People's Hospital

    Xingtai, Hebei

  • People's Hospital of Ningxia Hui Autonomous Region Affiliated to Ningxia Medical University

    Yinchuan, Ningxia

  • Central China Fuwai Hospital of Zhengzhou University

    Zhengzhou, Henan

  • Zhengzhou Central Hospital Affiliated to Zhengzhou University

    Zhengzhou, Henan

  • Zibo Central Hospital Affiliated to Binzhou Medical College

    Zibo, Shandong

  • Affiliated Zunhua People's Hospital of North China University of Science and Technology

    Zunhua, Hebei

Other trials in China

About this study

Official title: COMParison of the EffecT of mEdication Therapy: Anticoagulation Versus Anti-platelet Versus Migraine Therapy in Alleviating Migraine With Patent Foramen Ovale

Migraine attack is an episodic disorder that affects approximately 12% of the population. Previous studies have shown that 41-48% of migraineur have a combination of patent foramen ovale (PFO). Clinical observational studies have been linking medication therapies which include anticoagulation and anti-platelet therapy with the effectiveness in improving migraine symptoms and reducing the frequency of attacks in patients combined with a PFO. However, it has been unclear whether the effectiveness of anticoagulation or anti-platelet therapy outweigh the conventional migraine medication therapy, as a result, we designed a multi-center randomized clinical trial aiming to examine the effectiveness of anticoagulation versus anti-platelet versus migraine medication therapy in migraine patients with PFO and provide a clinical guidance for migraineur.

Being tested
Aspirin 300mg, Metoprolol 25mg, Clopidogrel 75mg, Rivaroxaban 20mg
Keywords
Migraine, Patent Foramen Ovale, Medication therapy
Medical subject headings
Foramen Ovale, Patent, Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aspirin 300mgDrug

    Aspirin 300 mg was administered once daily for 12 weeks.

  • Metoprolol 25mgDrug

    Metoprolol 25 mg was administered twice daily for 12 weeks.

  • Clopidogrel 75mgDrug

    Clopidogrel 75 mg was administered once daily for 12 weeks.

  • Rivaroxaban 20mgDrug

    Rivaroxaban 20 mg was administered once daily for 12 weeks.

Study groups in NCT05546320
Study groupRoleWhat they receive
Migraine Medication Group - Metoprolol GroupActive comparatorParticipants randomized to the active comparator group received metoprolol 25 mg orally twice daily for 12 weeks.
Receives: Drug: Metoprolol 25mg
Anticoagulation or anti-platelet medication Group 1 - Aspirin GroupExperimentalParticipants randomized to this group received aspirin 300 mg orally once daily for 12 weeks.
Receives: Drug: Aspirin 300mg
Anticoagulation or anti-platelet medication Group 2 - Clopidogrel GroupExperimentalParticipants randomized to this group received clopidogrel 75 mg orally once daily for 12 weeks.
Receives: Drug: Clopidogrel 75mg
Anticoagulation or anti-platelet medication Group 3 - Rivaroxaban GroupExperimentalParticipants randomized to this group received rivaroxaban 20 mg orally once daily for 12 weeks.
Receives: Drug: Rivaroxaban 20mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Responder rate

    Defined as the proportion of participants achieving a ≥50% reduction in the mean number of monthly migraine days or migraine attacks at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

Secondary outcomes (6)

  1. Change in monthly migraine days

    Change in the mean number of migraine days at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

  2. Change in monthly migraine attacks

    Change in the mean number of migraine attacks at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

  3. Reduction rate of migraine days

    Percentage reduction in the mean number of migraine days at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

  4. Reduction rate of migraine attacks

    Percentage reduction in the mean number of migraine attacks at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

  5. Complete migraine cessation

    Percentage of participants achieving complete migraine cessation during the 12-week treatment period.

    Measured: Weeks 9-12 post-randomization

  6. Migraine-specific quality of life (MSQ v2.1)

    Change in Migraine-Specific Quality of Life Questionnaire (MSQ version 2.1) scores at 12 weeks post-randomization compared to baseline.

    Measured: Baseline to 12 weeks post-randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2022
  2. Study start15 Oct 2022
  3. Primary completion26 Mar 2025
  4. Study completion26 Mar 2025

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05546320
Sponsor's protocol ID
2022-1758
Acronym
COMPETE
Status last verified
Apr 2026
First submitted
15 Sep 2022
Last updated
22 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Deidentified individual participant data underlying the results reported in this study will be made available upon the publication of the study.

Publications

  • Li Z, Dong J, Yan Y, Fang F, Wang C, Zhang F, Ouyang W, Wang S, Pan X. Study design and rationale of COMPETE: Comparison of the effect of medication therapy in alleviating migraine with patent foramen ovale. Am Heart J. 2024 Mar;269:1-7. doi: 10.1016/j.ahj.2023.12.011. Epub 2023 Dec 16.

    PubMed 38109984

  • Li Z, Wang C, Tang Y, Dong J, Dong J, Ouyang W, Zhang F, Pan J, Wan J, Han Y, Yang K, Liu Y, Wang Q, Li B, Tursun I, Shen Q, Li S, Lai H, Che H, Wang G, Ma Q, Hang Y, Huang K, Li Y, Wang P, Gao F, Liu W, Zhang H, Hu H, You T, Liu H, Chen L, Cheng Y, Zhang C, Wang R, Chen Z, Gong M, Fu Q, He C, Wang P, Shen C, Tan H, Zhang X, Zhang X, Zhang R, Wang Y, Pan X. Antithrombotic treatment for migraine in patients with patent foramen ovale: multicentre, randomised, active controlled, open label trial. BMJ. 2026 Jul 29;394:e100103. doi: 10.1136/bmj-2026-100103.

    PubMed 42526943

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aspirin 300mg, Metoprolol 25mg and Clopidogrel 75mg in people with Patent Foramen Ovale and Migraine, run by Chinese Academy of Medical Sciences, Fuwai Hospital at 39 sites in China.

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 6 inclusion and 15 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: finished, as of the sponsor's last update on 22 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 39 sites in China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Responder rate (time frame: Baseline to 12 weeks post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05546320, which also lists 2 linked publications.

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 22 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in