Seizure prophylaxis versus epilepsy prevention after acquired brain injury: a cross-sectional clinicaltrials.gov registry analysis, 2000–2026
Seizures after acquired brain injury pose distinct therapeutic questions: early seizure prophylaxis, treatment of acute symptomatic seizures, and late epilepsy prevention. These endpoints are often conflated, although early seizure suppression does not establish disease-modifying antiepileptogenesis, these end points are often confused. We performed a cross-sectional analysis of ClinicalTrials.gov records that were first posted from January 1, 2000, to June 18, 2026. Records retrieved through four disease-specific seizure-related searches were exported from the ClinicalTrials.gov web interface, deduplicated by NCT number, and adjudicated into a primary seizure-management or sensitivity/monitoring cohort. A purposively selected validation set of 269 potentially eligible or difficult-to-classify records underwent independent post-review classification by 2 reviewers who were blinded to each other’s responses. A prespecified secondary subset comprised completed primary-cohort trials evaluating pharmacologic interventions. The searches yielded 1,054 exported records and 878 unique records after deduplication. Final adjudication retained 85 primary cohort studies and 39 sensitivity/monitoring records. Brain tumor/neurosurgery (27/85, 31.8%) and traumatic brain injury (TBI) (23/85, 27.1%) predominated, whereas intracerebral hemorrhage and subarachnoid hemorrhage each had only 3 trials. Among the 44 completed or discontinued trials, 17 (38.6%) were discontinued. Among 26 completed trials eligible for results-reporting assessment, 11 (42.3%) had posted results, of which 10 (90.9%) were interventional drug trials. Only 3 of 15 completed pharmacologic trials had a late-prevention aim. Reviewer agreement ranged from 85.1% to 90.3%, with unweighted Cohen kappa values of 0.776–0.825. The seizure management pipeline after acquired brain injury registered on ClinicalTrials.gov is concentrated in brain tumor/neurosurgery and TBI, with sparse representation of hemorrhagic stroke and few completed pharmacologic trials targeting late epilepsy prevention. The registry findings support a clearer separation of the objectives of acute seizure prophylaxis, treatment of acute symptomatic seizures, and late epilepsy prevention. The etiology-specific design recommendations are presented as an author-proposed framework rather than empirical effectiveness conclusions. Not applicable. Only 3 of 15 completed pharmacologic trials had a late-prevention aim, indicating that the ClinicalTrials.gov-registered pipeline of completed antiepileptogenesis-oriented research remains limited. Of the 11 completed trials with posted ClinicalTrials.gov results, 10 were interventional drug trials, whereas completed nondrug trials rarely posted results. Intracerebral hemorrhage and subarachnoid hemorrhage each accounted for only 3 of 85 primary-cohort trials, and 17 of 44 completed-or-discontinued trials (38.6%) were discontinued.