PFO - Patent Foramen OvalePhase 3SPRINGNCT04946734
Effectivity and Safety of PFO Closure vs Medicine in Alleviating Migraine
A Phase 3 study testing PFO closure device, Aspirin and clopidogrel and Triptans in people with PFO - Patent Foramen Ovale and Migraine, run by Guangdong Provincial People's Hospital at 21 sites in China.
Trial summary
Effectivity and safety of PFO closure vs medicine in alleviating migraine （SPRING）: a multicenter, random, case control study Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- PFO - Patent Foramen Ovale, Migraine
- What is being tested?
- PFO closure device, Aspirin and clopidogrel and Triptans
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 21 sitesChina
- Study dates
- 12 Aug 2021to 6 Sep 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
China21 sites
China-Japan Friendship Hospital of Jilin University
Changchun, Jilin, 130033
Xiangya Hospital Central South University
Changsha, Hunan, 410008
Enshi Huiyi Hospital of Rheumatic Diseases
Enshi, Hubei, 445099
Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
Guangzhou, Guangdong, 510080
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
Guangdong Sanjiu Brain Hospital
Guangzhou, Guangdong, 510510
The Eighth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510630
The Eighth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Shenzhen, 518033
Huizhou First People's Hospital
Huizhou, Guangdong, 516003
Jiangmen Central Hospital
Jiangmen, Guangdong, 529000
The people's hospital of Leshan
Leshan, Sichuan, 614099
Nanjing First Hospital
Nanjing, Jiangsu, 210006
The First People's Hospital of Nanning
Nanning, Guangxi, 530022
Shangqiu First People's Hospital
Shangqiu, Henan, 476100
Shenzhen People's Hospital
Shenzhen, Guangdong, 518020
Shanxi Cardiovascular Hospital
Taiyuan, Shanxi, 030024
Tianjin Chest Hospital
Tianjin, Tianjin Municipality, 300222
Wuhan Asia Heart Hospital
Wuhan, Hubei, 430022
Zhongnan hospital of wuhan university
Wuhan, Hubei, 430071
Xiamen Cardiovascular Hospital Xiamen University
Xiamen, Fujian, 361016
Affiliated Hospital of Guangdong Medical University
Zhanjiang, Guangdong, 524001
About this study
Official title: 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
- Conditions
- PFO - Patent Foramen Ovale, Migraine
- Being tested
- PFO closure device, Aspirin and clopidogrel, Triptans
- Medical subject headings
- Foramen Ovale, Patent, Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PFO closure deviceDevice
Device PFO closure.
Aspirin and clopidogrelDrug
Aspirin 100mg qd for 6 months and clopidogrel 75mg qd administered for 1month after device implanted.
TriptansDrug
If migraine recurred, Triptans would be administered during the acute phase.
| Study group | Role | What they receive |
|---|---|---|
| Test Arm | Experimental | Device PFO closure Receives: Device: PFO closure device; Drug: Aspirin and clopidogrel; Drug: Triptans |
| Control Arm | Other | Drugs only Receives: Drug: Aspirin and clopidogrel; Drug: Triptans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete cessation of migraine
Primary Efficacy Endpoint
Measured: Month 12
Serious Adverse Event (SAE) related due to device, drug or study procedure
Primary Safety Endpoint
Measured: Month 12
Secondary outcomes (3)
Monthly migraine attacks
Mean change of monthly migraine attacks
Measured: 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
Measured: Baseline and Month 12
Responder rate
Percentage of subject with at least 50% reduction in monthly migraine attacks from baseline
Measured: Baseline and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start12 Aug 2021
- Primary completion6 Sep 2025 (estimated)
- Study completion6 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PFO - Patent Foramen OvaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhang Caojin, MD, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04946734
- Sponsor's protocol ID
- SPRING2021
- Acronym
- SPRING
- Status last verified
- Mar 2025
- First submitted
- 23 Jun 2021
- Last updated
- 12 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The deidentified participant data will be shared on a request basis.
Publications
Zi-Yang Y, Hezhi L, Dongling L, Ximeng W, Caojin Z; SPRING Investigators. Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail. BMC Cardiovasc Disord. 2024 Apr 5;24(1):198. doi: 10.1186/s12872-024-03866-3.
PubMed 38580946