VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa (VIGAB-STAT)

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

Study Overview

• Status: Completed
• Conditions: Coma; Status Epilepticus, Electrographic
• Intervention / Treatment: Drug: Vigabatrin Only Product

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label; 4500 mg of vigabatrin administered enterally	Drug: Vigabatrin Only Product; enteral medication administration, serial blood draws, and outcome assessment; Other Names: sabril, vigabatrone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Pharmacologic Outcome - Absorption	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.	3h
Primary Feasibility Outcome - Enrollment and Drug Delivery	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)	48 hours
Primary Feasibility Outcome - Visual Screening (Goldmann Perimetry)	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.	6 months
Primary Feasibility Outcome - Participants With Visual Screening for Taurine Levels	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.	0h, 72h and 168h following vigabatrin administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultra-early Vigabatrin Administration	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.	0h to 48h after vigabatrin admnistration
Secondary Pharmacologic Outcome: Elimination	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.	72h and 7 days following vigabatrin administration
PASE Onset Detection	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).	Determined at the time of connection to EEG monitoring

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Yale University; American Heart Association; Thomas Jefferson University
• Investigators: Principal Investigator: Carolina B Maciel, MD, MSCR, University of Florida

Publications and helpful links

General Publications

• Maciel CB, Teixeira FJP, Dickinson KJ, Spana JC, Merck LH, Rabinstein AA, Sergott R, Shan G, Miao G, Peloquin CA, Busl KM, Hirsch LJ. Early vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol. Neurol Res Pract. 2022 Jan 24;4(1):4. doi: 10.1186/s42466-022-00168-x.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): January 23, 2024

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: post-anoxic status epilepticus, cardiac arrest, nonconvulsive status epilepticus, coma, vigabatrin
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Status Epilepticus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; GABA Agents; Anticonvulsants; Vigabatrin
• Other Study ID Numbers: VIGAB-STAT IIa; IRB202003076 (Other Identifier: UF IRB-01); OCR40379 (Other Identifier: UF OnCore); PRO00031111 (Other Identifier: UFIRST); 20IPA35380013 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No