Study design and setting
PFO, PFOC-RE, Headache, epileptic seizures, anxiety, seizure, epilepsy, RLS, depression
EPILEPSY, ADVERSE EVENTS, EPILEPTIC SEIZURE, WEST, SECONDARY, EPILEPSY, EVENTS
This prospective, open-label, randomized, parallel-controlled clinical trial is conducted in the Epilepsy Center at the West China Hospital of Sichuan University. This study aims to evaluate the efficacy and safety of PFO closure for relieving epileptic seizures in patients with refractory epilepsy accompanied by PFO of second-grade or higher levels of RLS (PFOC-RE). The trial was registered on November 11, 2022, and the enrollment of all participants began on December 1, 2022. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2200065681).After completing clinical screening and signing an informed consent form, all participants are randomized in a 1:1 ratio into the intervention or control group. Subjects assigned to the intervention group will undergo a PFO closure procedure and receive antiplatelet therapy for 24 weeks, while those in the control group will only receive antiplatelet therapy for 24 weeks, which is consistent with the medication regimen of the intervention group. All participants will be followed-up for 48 weeks. During the follow-up period, seizure characteristics including frequency, duration, severity, quality of life, and adverse safety events will be recorded to evaluate the efficacy and safety of the trial. The overall design flowchart is shown in Fig. 
PFOC-RE Trial design flow chart. Note: PEO, primary efficacy outcome; SEO, secondary efficacy outcome; AE, adverse events; SAE, serious adverse events; PSQI, Pittsburgh sleep quality index scale; HDRS, Hamilton depression rating scale; HAMA, Hamilton anxiety scale; MoCA, Montreal cognitive assessment; HIT-6, Headache impact test; QOLIE-31, Quality of life in epilepsy inventory