VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa

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)

Time frame: 48 hours

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.

Time frame: 0h, 72h and 168h following vigabatrin administration

Population: At the 72h timepoint following vigabatrin administration, data for only 5 of the six subjects was analyzed due to the death of one subject before the 72h timepoint. At 168h, data for only 2 of the six subjects was analyzed due to death of four subjects.

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.

Time frame: 6 months

Population: The 6 month follow-up could not be completed for any of the 6 enrolled subjects due to in-hospital mortality

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.

Time frame: 3h

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).

Time frame: Determined at the time of connection to EEG monitoring

Population: The study did not enroll patients with PASE onset preceding the initiation of EEG monitoring. However, as a secondary exploratory outcome, we characterized the number of PASE-onset misses by determining the number of screen-failed patients, whose reason for screen failure was PASE onset preceding EEG monitoring initiation.

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.

Time frame: 72h and 7 days following vigabatrin administration

Population: 72 hours after vigabatrin administration, vigabatrin concentration draws were done for only 4 of the 6 subjects, due to the death of 2 subjects. Both the subjects that died had CrCl\<30 ml/min. All 4 of the subjects analyzed had CrCl\>30 ml/min. Therefore, the results could not be stratified based on creatinine clearance level.~7 days after vigabatrin administration, vigabatrin concentration draws were completed for only 2 of the six subjects, due to the death of the other 4 subjects.

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.

Time frame: 0h to 48h after vigabatrin admnistration