Effectivity and Safety of PFO Closure Vs Medicine in Alleviating Migraine (SPRING)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine; PFO - Patent Foramen Ovale
• Intervention / Treatment: Device: PFO closure device; Drug: Aspirin and clopidogrel; Drug: Triptans

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361016
      • Xiamen Cardiovascular Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510510
      • Guangdong Sanjiu Brain Hospital
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
    • Guangzhou, Guangdong, China, 510630
      • The Eighth Affiliated Hospital, Sun Yat-sen University
    • Huizhou, Guangdong, China, 516003
      • Huizhou First People's Hospital
    • Jiangmen, Guangdong, China, 529000
      • Jiangmen Central Hospital
    • Shenzhen, Guangdong, China, 518020
      • ShenZhen People's Hospital
    • Zhanjiang, Guangdong, China, 524001
      • Affiliated Hospital Of Guangdong Medical University
  • Guangxi
    • Nanning, Guangxi, China, 530022
      • The First People's Hospital of Nanning
  • Henan
    • Shangqiu, Henan, China, 476100
      • Shangqiu First People's Hospital
  • Hubei
    • Enshi, Hubei, China, 445099
      • Enshi Huiyi Hospital of Rheumatic Diseases
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430022
      • Wuhan Asia Heart Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
  • Jilin
    • Changchun, Jilin, China, 130033
      • China-Japan friendship Hospital of Jilin university
  • Shanxi
    • Taiyuan, Shanxi, China, 030024
      • Shanxi Cardiovascular Hospital
  • Shenzhen
    • Guangzhou, Shenzhen, China, 518033
      • The Eighth Affiliated Hospital, Sun Yat-sen University
  • Sichuan
    • Leshan, Sichuan, China, 614099
      • The people's hospital of Leshan
  • Tianjin
    • Tianjin, Tianjin, China, 300222
      • Tianjin Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Presence of PFO with right-to-left shunt, confirmed by Transthoracic.
2. Echocardiography (TTE) or transesophageal echocardiography (TEE) with a bubble study.
3. Bubble study positive confirmed by transcranial doppler.
4. Subject is diagnosed of migraine.
5. Subject signs an informed Consent Form and is willing to participate in follow-up visits

Exclusion Criteria:

1. Subject is diagnosed of headache with clear etiology.
2. Subject had cerebral hemorrhage, bleeding events in other organs within 3 months or was in high risk of bleeding.
3. Brain CT/MR showed ischemic lesions.
4. Subject is diagnosed of hepatic insufficiency: ALT or AST>3×ULN at the screening visit.
5. Subject is diagnosed of moderate to severe renal insufficiency: eGFR<30ml/min/1.73m2 at the screening visit.
6. Subject has uncontrolled arrhythmia with clinical significance within 90 days.
7. Subject is diagnosed of unstable angina, severe coronary atherosclerosis or myocardial infarction within 90 days.
8. Subject is diagnosed of pulmonary artery embolism, peripheral artery embolism or deep Vein Thrombosis.
9. Subject cannot follow the study procedure due to other acute or chronic diseases.
10. Subject is pregnant or lactating.
11. Subject is under other RCT.
12. Subject has a life expectancy <1 year.
13. Subject cannot follow the study procedure due to other reasons in the opinion of the investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2021
• Primary Completion (Estimated): September 6, 2025
• Study Completion (Estimated): September 6, 2025

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 9, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Headache Disorders, Primary; Headache Disorders; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects; Migraine Disorders; Foramen Ovale, Patent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin
• Other Study ID Numbers: SPRING2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The deidentified participant data will be shared on a request basis.

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