Effectivity and Safety of PFO Closure vs Medicine in Alleviating Migraine

Study Overview
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Brief Summary
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Effectivity and safety of PFO closure vs medicine in alleviating migraine （SPRING）: a multicenter, random, case control study

Official Title
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Effectivity and Safety of PFO Closure vs Medicine in Alleviating Migraine （SPRING）: a Multicenter, Random, Case Control Study

Conditions
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PFO - Patent Foramen Ovale, Migraine

Intervention / Treatment
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* Device: PFO closure device
* Drug: Aspirin and clopidogrel
* Drug: Triptans


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of PFO with right-to-left shunt, confirmed by Transthoracic. Echocardiography (TTE) or transesophageal echocardiography (TEE) with a bubble study. Bubble study positive confirmed by transcranial doppler. Subject is diagnosed of migraine. Subject signs an informed Consent Form and is willing to participate in follow-up visits Exclusion Criteria: Subject is diagnosed of headache with clear etiology. Subject had cerebral hemorrhage, bleeding events in other organs within 3 months or was in high risk of bleeding. Brain CT/MR showed ischemic lesions. Subject is diagnosed of hepatic insufficiency: ALT or AST>3×ULN at the screening visit. Subject is diagnosed of moderate to severe renal insufficiency: eGFR<30ml/min/1.73m2 at the screening visit. Subject has uncontrolled arrhythmia with clinical significance within 90 days. Subject is diagnosed of unstable angina, severe coronary atherosclerosis or myocardial infarction within 90 days. Subject is diagnosed of pulmonary artery embolism, peripheral artery embolism or deep Vein Thrombosis. Subject cannot follow the study procedure due to other acute or chronic diseases. Subject is pregnant or lactating. Subject is under other RCT. Subject has a life expectancy <1 year. Subject cannot follow the study procedure due to other reasons in the opinion of the investigators.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Arm<br>Device PFO closure | Device: PFO closure device<br>* Device PFO closure.<br>Drug: Aspirin and clopidogrel<br>* Aspirin 100mg qd for 6 months and clopidogrel 75mg qd administered for 1month after device implanted.<br>Drug: Triptans<br>* If migraine recurred, Triptans would be administered during the acute phase.<br>|
| Other: Control Arm<br>Drugs only | Drug: Aspirin and clopidogrel<br>* Aspirin 100mg qd for 6 months and clopidogrel 75mg qd administered for 1month after device implanted.<br>Drug: Triptans<br>* If migraine recurred, Triptans would be administered during the acute phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete cessation of migraine | Primary Efficacy Endpoint | Month 12 | 
| Serious Adverse Event (SAE) related due to device, drug or study procedure | Primary Safety Endpoint | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly migraine attacks | Mean change of monthly migraine attacks | Baseline and Month 12 | 
| Monthly migraine days | Mean change of monthly migraine days. Monthly migraine days = migraine attacks in one month × average time period per attacks (hours) /24 hours | Baseline and Month 12 | 
| Responder rate | Percentage of subject with at least 50% reduction in monthly migraine attacks from baseline | Baseline and Month 12 |