Percutaneous Repair for Drug - Resistant Epilepsy by Intervention of Closing the Patent Foramen Ovale（PREDICT-PFO Trial） (PREDICT-PFO)

Efficacy and Safety of Percutaneous Foramen Ovale Closure in Adult Patients with Drug-resistant Epilepsy and Patent Foramen Ovale: a Randomized Controlled Trial

Patent foramen ovale (PFO) is the most common cause of right-to-left shunt (RLS) in the adult heart, with a prevalence of approximately 25% in the general population. Extensive research has demonstrated an association between PFO and neurological conditions such as cryptogenic stroke, migraine, and sleep apnea syndrome, and it is even considered a potential root cause of these disorders. However, the mechanisms by which PFO contributes to neurological diseases remain unclear. In our preliminary clinical work, we have observed a strong correlation between PFO and epilepsy, and PFO closure has shown some efficacy in reducing seizure frequency. The aim of this study is to further investigate the efficacy and safety of PFO closure in patients with drug-resistant epilepsy.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy (treatment Refractory)
• Intervention / Treatment: Device: patent foramen ovale closure

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lei Chen; Phone Number: +8618980605819; Email: leilei_25@126.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • WestChina Hospital
      • Contact: Phone Number: +8619980483686

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 60 years, with no gender restrictions;
2. Diagnosis of epilepsy in accordance with the International League Against Epilepsy (ILAE) criteria (2014 edition);
3. Drug-resistant epilepsy, defined as failure to achieve sustained seizure freedom despite appropriate selection and tolerability of at least two antiseizure medications (monotherapy or combination therapy) for a minimum of six months;
4. Diagnosis of patent foramen ovale (PFO) meeting the criteria established by the American Society of Echocardiography (ASE) and the Society for Cardiovascular Angiography and Interventions (SCAI) (2015 edition), with right-to-left shunting (RLS) of grade II or higher upon Valsalva maneuver, as assessed by contrast-enhanced echocardiography;
5. Stable antiseizure medication regimen for at least four weeks prior to screening, with willingness to maintain a stable regimen throughout the study period;
6. At least one documented seizure episode during a six-week screening period (with a minimum of four weeks of effective seizure diary recordings) and a retrospective self-reported history of at least 12 seizures in the year preceding screening;
7. Ability to independently or with caregiver assistance complete a seizure diary and comply with clinical data collection and required medical examinations;
8. Willingness to undergo the investigational treatment and voluntary provision of written informed consent.

Exclusion Criteria:

1. Patients diagnosed with epilepsy of a known etiology, including infectious, metabolic, immune, genetic, or structural causes;
2. History of stroke or psychogenic nonepileptic seizures (PNES);
3. History of epilepsy surgery or implantable neurostimulation therapy, or planned epilepsy surgery, neurostimulation therapy, ketogenic diet therapy, or other antiseizure interventions during the study period;
4. Presence of structural cardiac abnormalities other than patent foramen ovale (PFO), such as moderate or severe valvular regurgitation or pulmonary hypertension;
5. Presence of severe central nervous system (CNS) diseases, including acute cerebrovascular disease, intracranial tumors, intracranial infections, or progressive CNS disorders;
6. Evidence of vascular puncture site infection or difficulty with puncture as assessed by transesophageal echocardiography combined with contrast-enhanced right heart echocardiography;
7. Documented contraindications to antiplatelet therapy;
8. Presence of severe psychiatric disorders, such as schizophrenia, bipolar disorder, or severe depression or anxiety;
9. History of alcohol or other substance abuse;
10. Severe dysfunction of vital organs (heart, lungs, liver, kidneys) deemed by the investigator to pose a risk to the participant or impair the participant's ability to complete the study;
11. Pregnant or breastfeeding women, or women planning to conceive during the study period;
12. Participation in another interventional clinical trial within three months prior to signing the informed consent form, current participation in another interventional trial, or plans to participate in another interventional trial during the study period; inability to comply with follow-up due to travel or relocation;
13. Any other condition that the investigator determines makes the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group
Experimental: Operation group; patent foramen ovale closure	Device: patent foramen ovale closure; patent foramen ovale closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage decrease in seizure frequency compared to baseline period	Percentage decrease in seizure frequency compared to baseline period	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage decrease in mean duration of seizures from baseline period	Percentage decrease in mean duration of seizures from baseline period	Week 48
Percentage of decrease from baseline in Epilepsy Severity	Percentage of decrease from baseline in Epilepsy Severity Scale score (NHS3)	Week 48
Percentage improvement from baseline in Quality of Life for Patients with Epilepsy	Percentage improvement from baseline in Quality of Life Rating Scale for Patients with Epilepsy (QOLIE-31)	Week 48
The maximum number of observation days without sustained epileptic seizures during the follow-up observation period	The maximum number of observation days without sustained epileptic seizures during the follow-up observation period	Up to 48 weeks
The proportion of subjects whose seizure frequency decreased by more than 50% compared to the baseline period	The proportion of subjects whose seizure frequency decreased by more than 50% compared to the baseline period	Week 48
The proportion of subjects whose average duration of epileptic seizures decreased by more than 50% compared to the baseline period	The proportion of subjects whose average duration of epileptic seizures decreased by more than 50% compared to the baseline period	Week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scores of Hamilton Anxiety Scale (HAMA)	The severity of anxiety	Week 24 and week 48
Scores of Hamilton Depression Scale (HAMD)	The severity of depression	Week 24 and week 48
Scores of MMSE	The severity of cognitive decline	Week 24 and week 48
Scores of MoCA	The severity of cognitive decline	Week 24 and week 48
Scores of Headache Impact Test-6	The severity of migraine	Week 24 and week 48
Scores of Migraine-SpecificQuality-of-Life Questionnaire	The severity of migraine	Week 24 and week 48
Scores of Pittsburgh Sleep Quality Index	sleep quality	Week 24 and week 48
Incidence rate of adverse reactions	Incidence rate of adverse reactions	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Sichuan University

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

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

• Keywords: patent foramen ovale; epielpsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects; Epilepsy; Foramen Ovale, Patent
• Other Study ID Numbers: HX20242572; ZYYC23011 (Other Grant/Funding Number: Lei Chen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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