VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa

Phase 2

Completed

Brief Summary: This is a pilot trial of a single loading dose of vigabatrin in post-anoxic status epilepticus.

Detailed Description: This pilot trial aims to demonstrate the feasibility of enteral administration of a single load of vigabatrin within targeted 48 hours of post-anoxic status epilepticus onset in unconscious survivors of cardiac arrest undergoing targeted temperature management. The load of VGB is in addition to the load of a commonly used intravenous second-line therapy given at the discretion of the treating neurologist. Serial blood tests will be obtained, including vigabatrin levels, taurine levels, neuron specific enolase, light chain neurofilament, and glial fibrillary acidic protein. In survivors that regain consciousness and survive to follow up, 6 months visual field perimetry will be obtained.

Recruitment & Eligibility

Inclusion Criteria

age ≥ 18 years
non-traumatic cardiac arrest (regardless of non-perfusing rhythm, etiology, or location of arrest) in whom the decision to treat unequivocal electrographic status epilepticus (as defined by the American Clinical Neurophysiology Society: having generalized spike/sharp-wave discharges ≥ 3Hz or any evolving pattern reaching > 4Hz, lasting ≥ 10 minutes, or comprising > 50% of any hour of recording) has been made
requiring anesthetic infusion for any reason
have reliable arterial access for frequent blood sampling
established enteral access within 48h of post-anoxic status epilepticus onset.

Exclusion Criteria

prior history of generalized epilepsy
history of gastrointestinal surgery within the last 21 days
pregnancy
status epilepticus onset preceding initiation of electroencephalography monitoring

Arm && Interventions

Group	Intervention	Description
Open label	Vigabatrin Only Product	4500 mg of vigabatrin administered enterally

Primary Outcome Measures

Name	Time	Method
Primary Pharmacologic Outcome - Absorption	3h	By analyzing serial vigabatrin levels including baseline, we characterized vigabatrin absorption; the target was to achieve a detectable vigabatrin level in the serum of ≥ 80% of enrolled subjects by 3 hours post-load.
Primary Feasibility Outcome - Visual Screening (Goldmann Perimetry)	6 months	We planned to obtain Goldmann perimetry testing in the subjects who could cooperate at the 6 months follow-up. Our goal was to have reliable visual field perimetry in ≥ 80% of survivors who regained consciousness following index hospitalization.
Primary Feasibility Outcome - Participants With Visual Screening for Taurine Levels	0h, 72h and 168h following vigabatrin administration	We obtained serial taurine levels during ICU stay at time 0h, 72h and 168h following vigabatrin administration. Our goal was to achieve a 90% completion rate for taurine levels.
Primary Feasibility Outcome - Enrollment and Drug Delivery	48 hours	We looked at the ability to deliver vigabatrin within 48 hours of PASE onset in ≥ 80% of enrolled subjects. Vigabatrin dose was adjusted according to renal functioning (CrCl\>50 ml/min: 4500 mg, CrCl 30-50 ml/min: 2250 mg, CrCl\<30 ml/min: 1125 mg)

Secondary Outcome Measures

Name	Time	Method
Secondary Pharmacologic Outcome: Elimination	72h and 7 days following vigabatrin administration	By analyzing serial VGB levels, we characterized drug elimination. We anticipated subjects with normal renal function would have undetectable vigabatrin levels by 72 hours, and those with creatinine clearance less than 30 mL/min would have detectable VGB levels at 72 hours. We anticipated undetectable vigabatrin levels in all subjects by 7 days regardless of their renal function.
Ultra-early Vigabatrin Administration	0h to 48h after vigabatrin admnistration	We tracked the proportion of enrolled subjects who received a vigabatrin load within 12 and 24 hours of PASE onset to explore the possibility of ultra-early administration of vigabatrin in subsequent phases.
PASE Onset Detection	Determined at the time of connection to EEG monitoring	We tracked the proportion of subjects in whom PASE was present upon connection to EEG (onset misses) to explore alternatives to allow prompt EEG monitoring following the return of spontaneous circulation (ROSC).