Trial Outcomes & Findings for VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa (NCT NCT04772547)

Last Updated: 2024-07-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Results posted on

2024-07-23

Participant Flow

The study recruitment occurred from September 2021 until June 2023 at the University of Florida, Shands Hospital. All patients with cardiac arrest requiring continuous EEG (cEE) monitoring were screened for eligibility.

A total of 161 cardiac arrest patients requiring continuous EEG monitoring were screened for eligibility. Of the 8 patients deemed eligible, 75% (n=6) were enrolled.

Participant milestones

Participant milestones
Measure	Open Label Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrcL 30-50 ml/min: 2,250 mg; Crcl\< 30 ml/min: 1,125 mg)
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label n=6 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrcL 30-50 ml/min: 2250 mg; Crcl\< 30 ml/min: 1125 mg)
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
BMI	33.22 kg/m^2 STANDARD_DEVIATION 13.11 • n=5 Participants
Creatinine Clearance (CrCl) CrCl >50 ml/min	2 Participants n=5 Participants
Creatinine Clearance (CrCl) CrCl 30-50 ml/min	2 Participants n=5 Participants
Creatinine Clearance (CrCl) CrCl <30 ml/min	2 Participants n=5 Participants
Weight	88.03 kg STANDARD_DEVIATION 32.12 • n=5 Participants
Vigabatrin Dose Administered 4500 mg	2 Participants n=5 Participants
Vigabatrin Dose Administered 2250 mg	2 Participants n=5 Participants
Vigabatrin Dose Administered 1125 mg	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3h

Outcome measures

Outcome measures
Measure	Open Label n=6 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
Primary Pharmacologic Outcome - Absorption Detectable drug level 3h post-administration	6 Participants
Primary Pharmacologic Outcome - Absorption Undetectable drug level 3h post-administration	0 Participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Open Label n=6 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
Primary Feasibility Outcome - Enrollment and Drug Delivery Vigabatrin administered within 48h of PASE onset	6 Participants
Primary Feasibility Outcome - Enrollment and Drug Delivery Vigabatrin not administered within 48h of PASE onset	0 Participants

PRIMARY outcome

Timeframe: 6 months

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

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Open Label n=6 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
Primary Feasibility Outcome - Participants With Visual Screening for Taurine Levels Taurine levels collected at 0h	6 Participants
Primary Feasibility Outcome - Participants With Visual Screening for Taurine Levels Taurine levels collected at 72h	4 Participants
Primary Feasibility Outcome - Participants With Visual Screening for Taurine Levels Taurine levels collected at 168h	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Open Label n=6 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
Ultra-early Vigabatrin Administration within 12h of PASE onset	1 Participants
Ultra-early Vigabatrin Administration within 12-24h of PASE onset	3 Participants
Ultra-early Vigabatrin Administration within 24-48h of PASE onset	2 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Open Label n=4 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
Secondary Pharmacologic Outcome: Elimination Undetectable vigabatrin concentration at 72h	2 Participants
Secondary Pharmacologic Outcome: Elimination Detectable vigabatrin concentration at 72h	2 Participants
Secondary Pharmacologic Outcome: Elimination Undetectable vigabatrin concentration at 7 days	2 Participants
Secondary Pharmacologic Outcome: Elimination Detectable vigabatrin concentration at 7 days	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Open Label n=161 Participants Vigabatrin administered enterally with serial blood draws and outcome assessment. Drug dose adjusted according to renal function.(CrCl\>50 ml/min: 4500 mg; CrCl 30-50 ml/min: 2,250 mg; CrCl\< 30 ml/min: 1,125 mg)
PASE Onset Detection	8 Participants

Adverse Events

Open Label

Serious events: 0 serious events

Other events: 0 other events

Deaths: 6 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Carolina B. Maciel

University of Florida

Phone: (352) 273-5550

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place