VIGABatrin in Post-anoxic STATus Epilepticus - Phase IIa

NCT04772547 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: VIGAB-STAT IIaIRB202003076OCR40379PRO0003111120IPA35380013
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Status Epilepticus, Electrographic; Coma

Keywords

post-anoxic status epilepticus, cardiac arrest, nonconvulsive status epilepticus, coma, vigabatrin

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Ultra-early Vigabatrin Administration

  0h to 48h after vigabatrin admnistration

• Secondary Pharmacologic Outcome: Elimination

  72h and 7 days following vigabatrin administration

• PASE Onset Detection

  Determined at the time of connection to EEG monitoring

Study Arms (1)

Open label

EXPERIMENTAL

4500 mg of vigabatrin administered enterally

Drug: Vigabatrin Only Product

Interventions

Vigabatrin Only Product DRUG

enteral medication administration, serial blood draws, and outcome assessment

Also known as: sabril, vigabatrone

Open label

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead
• Yale University: collaborator
• Thomas Jefferson University: collaborator
• American Heart Association: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (1)

• 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.

  PMID: 35067230 DERIVED

MeSH Terms

Conditions

Status Epilepticus; Coma; Heart Arrest

Interventions

Vigabatrin

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

We could not characterize the exploratory safety outcome in our subjects. We aimed to detect rates of retinopathy on vision loss screening via Goldmann perimetry upon regain of consciousness, ICU discharge, and 6 months, in addition to long-term visual screening at 6 months via Visual Function Questionnaire 25 (VFQ-25). However, all six patients enrolled in the trial did not regain consciousness or survive through the follow-up period. So, the assessments could not be performed.

Results Point of Contact

• Title: Dr. Carolina B. Maciel
• Organization: University of Florida

carolina.maciel@ufl.edu

(352) 273-5550

Study Officials

• Carolina B Maciel, MD, MSCR

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Participants are unconscious, thus, inherently blinded to the intervention. All the endpoints are objective and will be assessed by a blinded investigator to the timing of vigabatrin administration.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: pilot feasibility trial of pharmacokinetics of drug absorption

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: February 26, 2021
• Study Start: September 22, 2021
• Primary Completion: June 7, 2023
• Study Completion: January 23, 2024
• Last Updated: July 23, 2024
• Results First Posted: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)