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Completed

NCT Number: NCT05546320

Comparison of the Effect of Medication 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.

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Key information

Conditions

Patent Foramen Ovale Brain Diseases Cardiovascular Abnormalities Cardiovascular Diseases Central Nervous System Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Foramen Ovale, Patent Headache Disorders Headache Disorders, Primary Heart Defects, Congenital Heart Diseases Heart Septal Defects Heart Septal Defects, Atrial Migraine Migraine Disorders Nervous System Diseases

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

Aspirin 300mg

Drug

Aspirin 300 mg was administered once daily for 12 weeks.

Metoprolol 25mg

Drug

Metoprolol 25 mg was administered twice daily for 12 weeks.

Clopidogrel 75mg

Drug

Clopidogrel 75 mg was administered once daily for 12 weeks.

Rivaroxaban 20mg

Drug

Rivaroxaban 20 mg was administered once daily for 12 weeks.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Complete migraine cessation

    Time frame: Weeks 9-12 post-randomization

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

  6. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

Sponsors and collaborators

Lead sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Other

Registry information

Official study title

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

Acronym: COMPETE

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Sep 19, 2022
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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