Clinical trial NCT05000320: VIGAB-BIOSTAT: Neuronal Injury Panel Substudy
Official title: VIGAB-BIOSTAT: Neuronal Injury Panel Substudy
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Status Epilepticus
Cardiac Arrest With Successful Resuscitation
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2021-08-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults 18-80 years of age suffering from post anoxic status epilepticus (PASE)

Brief summary: The purpose of this substudy is to collect and analyze control data to characterize the degree of neuronal injury in PASE patients who have not received vigabatrin to later compare with patients who received this therapy and expand data on the utility of the neuronal injury panel for neuroprognostication. Data from this cohort will be compared with the data generated by the treatment cohort in the main VIGAB-STAT study.

Detailed description: Post anoxic status epilepticus (PASE) is the development of intractable seizures in the post-cardiac arrest period once return of spontaneous circulation (ROSC) has been achieved. Historically, this condition has resulted in nearly 100% mortality, and the subset of patients diagnosed with PASE has been excluded from previous therapeutic trials in status epilepticus. The administration of vigabatrin, a GABA-ergic medication that blocks GABA catabolism, is being investigated as an adjunctive therapy to improve neurologic outcomes in this patient population through the VIGAB-STAT program at the University of Florida.

Neuroprognostication in cardiac arrest patients remains imprecise. Outcomes following cardiac arrest depend on a multitude of factors, from details of cardiac arrest (e.g., downtime and rhythm on arrest) to other factors that influence secondary brain injury-all of which are hard to ascertain from objective clinical and laboratory data. Neuronal and astroglial protein assays have been investigated in this patient population as a novel method of quantifying the degree of neuronal injury and may serve as an objective informant of ongoing secondary brain injury, thus being a helpful neuroprognostic tool. This assay can also demonstrate objectively if a neuroprotectant therapy mitigates secondary brain injury and decreases the overall hypoxic-brain injury burden. However, normative data on these assays on post-cardiac arrest patients suffering PASE are lacking.

Eligibility criteria: Inclusion Criteria:

* To be included in the study, subjects must be 18 - 80 years of age
* Non-traumatic cardiac arrest (regardless of non-perfusing rhythm, etiology, or location of arrest) in whom the decision to treat unequivocal electrographic SE (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
* Be enrolled and have the first specimen drawn within 48 hours of PASE onset.

Exclusion Criteria:

* Subjects must not have a prior history of generalized epilepsy
* Be pregnant or
* Have PASE onset preceding initiation of EEG monitoring.

Primary outcomes:
measure: Measure the degree of brain injury
timeFrame: Days 1 - 5
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Florida
name: Carolina Maciel, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Legriel S, Hilly-Ginoux J, Resche-Rigon M, Merceron S, Pinoteau J, Henry-Lagarrigue M, Bruneel F, Nguyen A, Guezennec P, Troche G, Richard O, Pico F, Bedos JP. Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era. Resuscitation. 2013 Mar;84(3):343-50. doi: 10.1016/j.resuscitation.2012.11.001. Epub 2012 Nov 9.
citation: Backman S, Westhall E, Dragancea I, Friberg H, Rundgren M, Ullen S, Cronberg T. Electroencephalographic characteristics of status epilepticus after cardiac arrest. Clin Neurophysiol. 2017 Apr;128(4):681-688. doi: 10.1016/j.clinph.2017.01.002. Epub 2017 Jan 21.
citation: Huesgen KW, Elmelige YO, Yang Z, Chowdhury MAB, Gul S, Maciel CB, Elie-Turenne MC, Becker TK, Cohen SA, Holland A, Montero C, Zhu T, Wang KK, Tyndall JA; Florida Cardiac Arrest Resource Team. Ultra-early serum concentrations of neuronal and astroglial biomarkers predict poor neurological outcome after out-of-hospital cardiac arrest-a pilot neuroprognostic study. Resusc Plus. 2021 Jun 8;7:100133. doi: 10.1016/j.resplu.2021.100133. eCollection 2021 Sep.
citation: Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018 Feb;18(2):165-180. doi: 10.1080/14737159.2018.1428089. Epub 2018 Jan 23.