Seizure prophylaxis versus epilepsy prevention after acquired brain injury: a cross-sectional clinicaltrials.gov registry analysis, 2000–2026

Abstract

Abstract Background Seizures after acquired brain injury create distinct therapeutic questions: early seizure prophylaxis, treatment of acute symptomatic seizures, and prevention of late epilepsy. These endpoints are often conflated, although early seizure suppression does not establish disease-modifying antiepileptogenesis. Methods We performed a cross-sectional ClinicalTrials.gov registry analysis of studies first posted from January 1, 2000, through June 18, 2026. Four disease-specific seizure-related search blocks were deduplicated by NCT number and adjudicated into a primary seizure-management cohort or sensitivity/monitoring cohort. Data were extracted from ClinicalTrials.gov export files and final adjudicated CTG Excel workbooks. In response to clinical-review priorities, we added NCT-specific extraction of completed pharmacologic trials, antiseizure medication or study-drug dosing when explicitly present in registry fields, seizure-control endpoints, follow-up windows, and clinical, EEG/cEEG/ECoG, and MRI/CT/imaging markers. Results Searches yielded 1,054 exported records; after removal of duplicate NCT numbers, 878 unique records were screened. Final adjudication retained 85 primary-cohort studies and 39 sensitivity/monitoring records; 754 records were excluded. Reviewer agreement was substantial to almost perfect across inclusion, disease category, seizure-focus category, and intervention type (kappa range, 0.787–0.897). Primary-cohort activity was concentrated in brain tumor/neurosurgery (27/85, 31.8%) and traumatic brain injury (23/85, 27.1%). Trial focus included late epilepsy prevention (26/85, 30.6%), acute seizure prophylaxis (25/85, 29.4%), acute symptomatic seizure treatment (23/85, 27.1%), and monitoring/characterization or other ASM-use studies (11/85, 12.9%). Drug/ASM interventions accounted for 46/85 (54.1%). Among 26 completed trials eligible for registry results-reporting assessment, 11 (42.3%) had posted results. Completed medication/study-drug trials were clinically heterogeneous, and explicit dose fields were sparse and NCT-specific. Conclusions The registered evidence-generating pipeline for seizures after acquired brain injury is clinically important but fragmented. Future trials should separate acute seizure suppression from late epilepsy prevention, enrich enrollment using etiology-specific seizure-risk markers, predefine how clinical seizures, EEG/cEEG/ECoG, and imaging guide prophylaxis decisions and duration, and improve dose-level and results reporting. Clinical trial registration Clinical trial number: not applicable. This manuscript is a cross-sectional registry analysis and was not itself a clinical trial. NCT01463033 is an included ClinicalTrials.gov registry record; its ClinicalTrials.gov first-posted/registration date was November 1, 2011.