Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT)

This Phase III, randomised, quadruple-masked trial (n=770) will evaluate the efficacy of adding low-dose (1 mg/kg) or high-dose (3 mg/kg) ketamine to levetiracetam (LEV) at 60 mg/kg in patients with benzodiazepine-refractory status epilepticus (SE). The primary aim is to determine whether this combination leads to more effective control of SE compared to levetiracetam alone, with the primary outcome being the termination of SE sustained for 60 minutes without additional anti-seizure medication. The trial will initially allocate participants equally among the three treatment arms for the first 350 subjects before transitioning to response-adaptive randomisation. The primary outcome will be assessed by evaluating improvements in consciousness and the absence of clinically apparent seizures at 60 minutes, or the absence of electrographic SE after 15 minutes in those with EEG monitoring. Secondary objectives include safety assessments and exploratory efficacy outcomes, particularly in the paediatric subpopulation. The study is set to begin in February 2026 and aims for completion by December 2029.