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
- Are there results?
- Not yet: the study is under way
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.
Show all 13Show fewer
- 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.
- More trials run by Guangdong Provincial People's HospitalThe sponsor's other registered studies.
- 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectivity and Safety of PFO Closure vs Medicine in Alleviating Migraine （SPRING）: a Multicenter, Random, Case Control Study
- ClinicalTrials.gov ID
- NCT04946734
- Acronym / sponsor ID
- SPRING / SPRING2021
- Conditions
- PFO - Patent Foramen Ovale, Migraine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Study start
- 12 Aug 2021 (actual)
- Primary completion
- 6 Sep 2025 (estimated)
- Study completion
- 6 Sep 2025 (estimated)
- First posted
- 1 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Effectivity and safety of PFO closure vs medicine in alleviating migraine （SPRING）: a multicenter, random, case control study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test Arm | Experimental | Device: PFO closure device, Drug: Aspirin and clopidogrel, Drug: TriptansDevice PFO closure |
| Control Arm | Other | Drug: Aspirin and clopidogrel, Drug: TriptansDrugs only |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PFO closure deviceDevice PFO closure. | Device | Test Arm |
| Aspirin and clopidogrelAspirin 100mg qd for 6 months and clopidogrel 75mg qd administered for 1month after device implanted. | Drug | Control Arm, Test Arm |
| TriptansIf migraine recurred, Triptans would be administered during the acute phase. | Drug | Control Arm, Test Arm |
Primary outcome
Complete cessation of migraine
Time frame: Month 12
Primary Efficacy Endpoint
Serious Adverse Event (SAE) related due to device, drug or study procedure
Time frame: Month 12
Primary Safety Endpoint
3 secondary outcomes
Monthly migraine attacks
Time frame: Baseline and Month 12
Monthly migraine days
Time frame: Baseline and Month 12
Responder rate
Time frame: Baseline and Month 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Derived from this study: PubMed 38580946Zi-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.
- Individual participant dataSharing planned: No. The deidentified participant data will be shared on a request basis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete cessation of migraine (time frame: Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04946734, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025.