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

April 17, 2026 updated by: Pan Xiangbin, Chinese Academy of Medical Sciences, Fuwai Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China
        • The First affiliated Hospital of Anhui Medical University
      • Hefei, Anhui, China
        • The First Affiliated Hospital of USTC
      • Suzhou, Anhui, China
        • Suzhou Hospital of Anhui Medical University
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Beijing Tiantan Hospital, Capital Medical University
      • Beijing, Beijing Municipality, China
        • National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences
    • Gansu
      • Lanzhou, Gansu, China
        • Gansu Provincial Hospital
      • Lanzhou, Gansu, China
        • The Second Affiliated Hospital of Lanzhou University
    • Guangdong
      • Guangzhou, Guangdong, China
        • Guangdong Provincial People's Hospital
      • Shenzhen, Guangdong, China
        • Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen Hospital
      • Shenzhen, Guangdong, China
        • The Seventh Affiliated Hospital of Sun Yat-sen University
    • Guangxi
      • Nanning, Guangxi, China
        • The First Affiliated Hospital, Guangxi Medical University
    • Guizhou
      • Guiyang, Guizhou, China
        • Guizhou Provincial People's Hospital
    • Hebei
      • Shijiazhuang, Hebei, China
        • Hebei General Hospital
      • Shijiazhuang, Hebei, China
        • The Second Hospital of Hebei Medical University
      • Xingtai, Hebei, China
        • Xingtai People's Hospital
      • Zunhua, Hebei, China
        • Affiliated Zunhua People's Hospital of North China University of Science and Technology
    • Heilongjiang
      • Daqing, Heilongjiang, China
        • Daqing Longnan Hospital
    • Henan
      • Nanyang, Henan, China
        • Nanyang Central Hospital
      • Shangqiu, Henan, China
        • Shangqiu First People's Hospital
      • Zhengzhou, Henan, China
        • Zhengzhou Central Hospital Affiliated to Zhengzhou University
      • Zhengzhou, Henan, China
        • Central China Fuwai Hospital of Zhengzhou University
    • Hubei
      • Wuhan, Hubei, China
        • Wuhan Asia Heart Hospital
      • Xiangyang, Hubei, China
        • Xiangyang Central Hospital
    • Jiangxi
      • Nanchang, Jiangxi, China
        • The Second Affiliated Hospital of Nanchang University
      • Nanchang, Jiangxi, China
        • Jiangxi Provincial People's Hospital Affiliated to Nanchang University
    • Liaoning
      • Dalian, Liaoning, China
        • Dalian Municipal Central Hospital
      • Dalian, Liaoning, China
        • Dalian University Affiliated Zhongshan Hospital
      • Shenyang, Liaoning, China
        • The Fourth People's Hospital of Shenyang
    • Ningxia
      • Yinchuan, Ningxia, China
        • People's Hospital of Ningxia Hui Autonomous Region Affiliated to Ningxia Medical University
    • Shandong
      • Jinan, Shandong, China
        • The Second Hospital, Cheeloo College of Medicine, Shandong University
      • Qingdao, Shandong, China
        • Qingdao Fuwai Cardiovascular Hospital
      • Zibo, Shandong, China
        • Zibo Central Hospital Affiliated to Binzhou Medical College
    • Shanxi
      • Taiyuan, Shanxi, China
        • First Hospital of Shanxi Medical University
    • Sichuan
      • Chengdu, Sichuan, China
        • West China Hospital of Sichuan University
      • Chengdu, Sichuan, China
        • The First Affiliated Hospital of Chengdu Medical College
      • Chengdu, Sichuan, China
        • Clinical Medical College and Affiliated Hospital of Chengdu University
    • Xinjiang
      • Ürümqi, Xinjiang, China
        • The Second Affiliated Hospital of Xinjiang Medical University
    • Yunnan
      • Kunming, Yunnan, China
        • The First Affiliated Hospital of Kunming Medical University
      • Kunming, Yunnan, China
        • Fuwai Cardiovascular Hospital of Yunnan Province

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

Participants must meet all of the following criteria:

  1. Aged 18 to 64 years at Visit 1.
  2. Diagnosis of migraine with or without aura confirmed by a neurologist, according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.
  3. 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.
  4. 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.
  5. Provision of written informed consent and willingness to comply with follow-up procedures.

Exclusion Criteria

Participants will be excluded if any of the following apply:

  1. Secondary headache attributable to other causes.
  2. History of transient ischemic attack, stroke, or intracranial hemorrhage.
  3. History of pacemaker implantation, atrial septal defect closure, or left atrial appendage closure.
  4. Right-to-left intracardiac shunt due to causes other than PFO.
  5. Contraindications to antiplatelet or anticoagulant therapy, including thrombocytopenia, major trauma, active bleeding, decompensated cirrhosis, or drug allergy.
  6. Contraindications to beta-blocker therapy, including hypotension, severe bradycardia, atrioventricular block, asthma, or drug allergy.
  7. Poorly controlled atrial fibrillation at Visit 1.
  8. Poorly controlled hypertension at Visit 1, defined as blood pressure >160/90 mmHg despite regular medication.
  9. Inability to maintain a headache diary or to reliably report headache symptoms.
  10. Use of anticoagulants (e.g., warfarin, rivaroxaban) or antiplatelet agents (e.g., aspirin, clopidogrel, ticagrelor) within 12 weeks prior to Visit 2.
  11. Use of metoprolol within 12 weeks prior to Visit 2.
  12. Pregnancy, intention to become pregnant during the study period, or planned elective surgery during the study period.
  13. Any condition that, in the investigator's opinion, may pose significant risk, confound study results, or interfere with participation.
  14. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Migraine Medication Group - Metoprolol Group
Participants randomized to the active comparator group received metoprolol 25 mg orally twice daily for 12 weeks.
Drug: Metoprolol 25mg
Metoprolol 25 mg was administered twice daily for 12 weeks.
Experimental: Anticoagulation or anti-platelet medication Group 1 - Aspirin Group
Participants randomized to this group received aspirin 300 mg orally once daily for 12 weeks.
Drug: Aspirin 300mg
Aspirin 300 mg was administered once daily for 12 weeks.
Experimental: Anticoagulation or anti-platelet medication Group 2 - Clopidogrel Group
Participants randomized to this group received clopidogrel 75 mg orally once daily for 12 weeks.
Drug: Clopidogrel 75mg
Clopidogrel 75 mg was administered once daily for 12 weeks.
Experimental: Anticoagulation or anti-platelet medication Group 3 - Rivaroxaban Group
Participants randomized to this group received rivaroxaban 20 mg orally once daily for 12 weeks.
Drug: Rivaroxaban 20mg
Rivaroxaban 20 mg was administered once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Responder rate
Time Frame: Baseline to 12 weeks post-randomization
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.
Baseline to 12 weeks post-randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in monthly migraine days
Time Frame: Baseline to 12 weeks post-randomization
Change in the mean number of migraine days at 12 weeks post-randomization compared to baseline.
Baseline to 12 weeks post-randomization
Change in monthly migraine attacks
Time Frame: Baseline to 12 weeks post-randomization
Change in the mean number of migraine attacks at 12 weeks post-randomization compared to baseline.
Baseline to 12 weeks post-randomization
Reduction rate of migraine days
Time Frame: Baseline to 12 weeks post-randomization
Percentage reduction in the mean number of migraine days at 12 weeks post-randomization compared to baseline.
Baseline to 12 weeks post-randomization
Reduction rate of migraine attacks
Time Frame: Baseline to 12 weeks post-randomization
Percentage reduction in the mean number of migraine attacks at 12 weeks post-randomization compared to baseline.
Baseline to 12 weeks post-randomization
Complete migraine cessation
Time Frame: Weeks 9-12 post-randomization
Percentage of participants achieving complete migraine cessation during the 12-week treatment period.
Weeks 9-12 post-randomization
Migraine-specific quality of life (MSQ v2.1)
Time Frame: Baseline to 12 weeks post-randomization
Change in Migraine-Specific Quality of Life Questionnaire (MSQ version 2.1) scores at 12 weeks post-randomization compared to baseline.
Baseline to 12 weeks post-randomization

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety Outcome Measures - Any adverse events
Time Frame: Baseline to 12 weeks post-randomization
Any undesirable medical condition occurring in a participant after initiation of the investigational medicinal products, regardless of its causal relationship with the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Adverse events related to investigational medicinal products
Time Frame: Baseline to 12 weeks post-randomization
Adverse events assessed by investigators as having a definite, probable, or possible causal relationship with the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Serious adverse events
Time Frame: Baseline to 12 weeks post-randomization
Events including death, life-threatening events, hospitalization or prolongation of hospitalization, permanent disability or damage, congenital anomaly or birth defect, or other medically significant events, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Serious adverse events related to investigational medicinal products
Time Frame: Baseline to 12 weeks post-randomization
Serious adverse events assessed by investigators as having a definite, probable, or possible causal relationship with the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Any bleeding events
Time Frame: Baseline to 12 weeks post-randomization
Bleeding events classified according to the Bleeding Academic Research Consortium criteria (types 1 to 5), assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Major bleeding events
Time Frame: Baseline to 12 weeks post-randomization
Bleeding events classified as Bleeding Academic Research Consortium type 3b, type 3c, or type 5, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Gastrointestinal symptoms
Time Frame: Baseline to 12 weeks post-randomization
Any discomfort or symptoms involving the gastrointestinal tract occurring after administration of the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Bradycardia
Time Frame: Baseline to 12 weeks post-randomization
Symptomatic reduction in heart rate occurring after administration of the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Hypotension
Time Frame: Baseline to 12 weeks post-randomization
Symptomatic reduction in blood pressure occurring after administration of the investigational medicinal products, assessed by investigators and adjudicated by the clinical event committee.
Baseline to 12 weeks post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese Academy of Medical Sciences, Fuwai Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xiangbin Pan, National Center for Cardiovascular Disease, China & Fuwai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 15, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 26, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 26, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 15, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 19, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022-1758

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual participant data underlying the results reported in this study will be made available upon the publication of the study.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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