Comparison of biodegradable and metal occluders in patients with PFO and migraine: study design and rationale of BioMetal Trial

Abstract

Background: The association between migraine and patent foramen ovale (PFO) has led to investigations into percutaneous PFO closure as a potential therapeutic avenue. While existing trials with metal occluders have shown promise in reducing migraine burden, concerns over long-term complications and the impact of metal devices on migraine exacerbation have prompted the development of biodegradable alternatives.

Methods: The Comparison of Biodegradable and Metal Occluders in Patients with PFO and Migraine (BioMetal) trial is a prospective, multicenter, single-blind, randomized controlled, superiority study comparing a biodegradable occluder with a nickel-titanium alloy occluder in PFO patients with medication-refractory migraine with aura (ClinicalTrials.gov Identifier: NCT06203873). A total of 400 participants will be enrolled, randomized 1:1 to receive either the biodegradable or metal devices, and followed up for 24 months post-randomization. The primary endpoint is the change in monthly migraine days at 12 months compared to baseline.

Discussion: The BioMetal trial aims to address the ongoing debate surrounding PFO closure for migraine relief by evaluating the efficacy and safety of biodegradable versus metal devices, with the goal of providing valuable insights into the optimal approach for PFO closure in PFO patients with medication-refractory migraine with aura. The potential implications extend beyond migraine management, highlighting the significance of biocompatible and sustainable materials in interventional cardiology. Completion of this study is anticipated to inform future clinical practice and guide therapeutic strategies in this complex condition.

Trial registration: ClinicalTrials.gov NCT06203873 ( https://clinicaltrials.gov/study/NCT06203873 ). Registered on January 3, 2024.

Keywords: Biodegradable occluder; Metal occluder; Migraine; Patent foramen ovale; Randomized controlled trial.

Fig. 1

Flowchart of BioMetal trial

Fig. 2

Schedule of enrolment, interventions, and trial assessments Abbreviations: AE/SAE, Adverse Event/Serious Adverse Event; cTEE, contrast Transesophageal Echocardiography; ECG, Electrocardiogram; MSQ v2.1, Migraine-Specific Quality of Life Questionnaire version 2.1; NA, Not Applicable; TEE, Transesophageal Echocardiography. a. Randomization will occur once the catheter passes through the PFO into the left atrium. b. Brain imaging screening included magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), computerized tomography (CT), and computed tomography angiography (CTA) conducted within 3 months prior to Visit 1 to identify any specific transient ischemic attacks, strokes, or intracranial hemorrhages. c. Assessments indicated in brackets [X] will be performed only for office visits. d. Demographic data collection includes date of birth, gender, and ethnicity. e. Medical history includes myocardial infarction, angina, smoking, hypertension, diabetes mellitus, hyperlipidemia, snoring, palpitations, psychiatric disorders, head trauma, contraceptive drugs use, cerebral infarction, TIA, peripheral vascular diseases, respiratory insufficiency, NYHA heart function, atrial fibrillation, other arrhythmias previous PCI and previous coronary artery bypass craft. f. Clinical laboratory determinations include hematology, biochemistry, coagulation parameters and urinalysis. g. For females of childbearing potential, urine pregnancy test will be performed at Visit 1. h. Vital signs include height, weight, sitting pulse, respiratory rate, and sitting blood pressure. Height and weight are measured only at Visit 1. If Visits 4 and 6 are conducted via telephone/WeChat, participants will report home self-test results. i. Physical examination includes general condition, neck (including thyroid), head, eyes, ears, nose, throat, lungs, heart, abdomen, nervous system, limbs, musculoskeletal system, superficial lymph nodes, skin, and others. j. Participants will take aspirin 100 mg daily combined with clopidogrel 75 mg daily for 3 months, followed by clopidogrel 75 mg daily for an additional 3 months. Administered immediately after procedure. k. Refer to the Headache Diary (see Supplemental Material). l. Participants will complete MSQ v2.1 on the e-Questionnaire application. m. Participants bring the Headache Diary to all office visits, particularly Visits 2, 3, 5, 7, and 8. If Visits 4 and 6 are via telephone/WeChat, participants self-report their Headache Diary data verbally or by transmitting photos via WeChat. Experienced neurologists review and evaluate the Headache Diaries in a blinded manner at Visits 2-8