Comparison of the Effect of Medication Therapy in Alleviating Migraine With Patent Foramen Ovale
COMPETE
COMParison of the EffecT of mEdication Therapy: Anticoagulation Versus Anti-platelet Versus Migraine Therapy in Alleviating Migraine With Patent Foramen Ovale
1 other identifier
interventional
1,000
1 country
39
Brief 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). 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2022
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 15, 2022
CompletedFirst Posted
Study publicly available on registry
September 19, 2022
CompletedStudy Start
First participant enrolled
October 15, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 26, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 26, 2025
CompletedApril 22, 2026
April 1, 2026
2.4 years
September 15, 2022
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Baseline to 12 weeks post-randomization
Secondary Outcomes (6)
Change in monthly migraine days
Baseline to 12 weeks post-randomization
Change in monthly migraine attacks
Baseline to 12 weeks post-randomization
Reduction rate of migraine days
Baseline to 12 weeks post-randomization
Reduction rate of migraine attacks
Baseline to 12 weeks post-randomization
Complete migraine cessation
Weeks 9-12 post-randomization
- +1 more secondary outcomes
Other Outcomes (9)
Safety Outcome Measures - Any adverse events
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Adverse events related to investigational medicinal products
Baseline to 12 weeks post-randomization
Safety Outcome Measures - Serious adverse events
Baseline to 12 weeks post-randomization
- +6 more other outcomes
Study Arms (4)
Migraine Medication Group - Metoprolol Group
ACTIVE COMPARATORParticipants randomized to the active comparator group received metoprolol 25 mg orally twice daily for 12 weeks.
Anticoagulation or anti-platelet medication Group 1 - Aspirin Group
EXPERIMENTALParticipants randomized to this group received aspirin 300 mg orally once daily for 12 weeks.
Anticoagulation or anti-platelet medication Group 2 - Clopidogrel Group
EXPERIMENTALParticipants randomized to this group received clopidogrel 75 mg orally once daily for 12 weeks.
Anticoagulation or anti-platelet medication Group 3 - Rivaroxaban Group
EXPERIMENTALParticipants randomized to this group received rivaroxaban 20 mg orally once daily for 12 weeks.
Interventions
Clopidogrel 75 mg was administered once daily for 12 weeks.
Rivaroxaban 20 mg was administered once daily for 12 weeks.
Aspirin 300 mg was administered once daily for 12 weeks.
Metoprolol 25 mg was administered twice daily for 12 weeks.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (39)
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
The First Affiliated Hospital of USTC
Hefei, Anhui, China
Suzhou Hospital of Anhui Medical University
Suzhou, Anhui, 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
Beijing, Beijing Municipality, China
Gansu Provincial Hospital
Lanzhou, Gansu, China
The Second Affiliated Hospital of Lanzhou University
Lanzhou, Gansu, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen Hospital
Shenzhen, Guangdong, China
The Seventh Affiliated Hospital of Sun Yat-sen University
Shenzhen, Guangdong, China
The First Affiliated Hospital, Guangxi Medical University
Nanning, Guangxi, China
Guizhou Provincial People's Hospital
Guiyang, Guizhou, China
Hebei General Hospital
Shijiazhuang, Hebei, China
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
Xingtai People's Hospital
Xingtai, Hebei, China
Affiliated Zunhua People's Hospital of North China University of Science and Technology
Zunhua, Hebei, China
Daqing Longnan Hospital
Daqing, Heilongjiang, China
Nanyang Central Hospital
Nanyang, Henan, China
Shangqiu First People's Hospital
Shangqiu, Henan, China
Central China Fuwai Hospital of Zhengzhou University
Zhengzhou, Henan, China
Zhengzhou Central Hospital Affiliated to Zhengzhou University
Zhengzhou, Henan, China
Wuhan Asia Heart Hospital
Wuhan, Hubei, China
Xiangyang Central Hospital
Xiangyang, Hubei, China
Jiangxi Provincial People's Hospital Affiliated to Nanchang University
Nanchang, Jiangxi, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
Dalian Municipal Central Hospital
Dalian, Liaoning, China
Dalian University Affiliated Zhongshan Hospital
Dalian, Liaoning, China
The Fourth People's Hospital of Shenyang
Shenyang, Liaoning, China
People's Hospital of Ningxia Hui Autonomous Region Affiliated to Ningxia Medical University
Yinchuan, Ningxia, China
The Second Hospital, Cheeloo College of Medicine, Shandong University
Jinan, Shandong, China
Qingdao Fuwai Cardiovascular Hospital
Qingdao, Shandong, China
Zibo Central Hospital Affiliated to Binzhou Medical College
Zibo, Shandong, China
First Hospital of Shanxi Medical University
Taiyuan, Shanxi, China
Clinical Medical College and Affiliated Hospital of Chengdu University
Chengdu, Sichuan, China
The First Affiliated Hospital of Chengdu Medical College
Chengdu, Sichuan, China
West China Hospital of Sichuan University
Chengdu, Sichuan, China
The Second Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, China
Fuwai Cardiovascular Hospital of Yunnan Province
Kunming, Yunnan, China
The First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, China
Related Publications (1)
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.
PMID: 38109984RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Xiangbin Pan
National Center for Cardiovascular Disease, China & Fuwai Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Open-label treatment allocation with blinded outcome assessment based on prospectively completed headache diaries reviewed by independent neurologists blinded to treatment assignment.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Project Manager
Study Record Dates
First Submitted
September 15, 2022
First Posted
September 19, 2022
Study Start
October 15, 2022
Primary Completion
March 26, 2025
Study Completion
March 26, 2025
Last Updated
April 22, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
Deidentified individual participant data underlying the results reported in this study will be made available upon the publication of the study.