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| ID | Type | Description | Link |
|---|---|---|---|
| IRB202003076 | Other Identifier | UF IRB-01 | |
| OCR40379 | Other Identifier | UF OnCore | |
| PRO00031111 | Other Identifier | UFIRST | |
| 20IPA35380013 | Other Grant/Funding Number | American Heart Association |
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| Name | Class |
|---|---|
| Yale University | OTHER |
| Thomas Jefferson University | OTHER |
| American Heart Association | OTHER |
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This is a pilot trial of a single loading dose of vigabatrin in post-anoxic status epilepticus.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open label | Experimental | 4500 mg of vigabatrin administered enterally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vigabatrin Only Product | Drug | enteral medication administration, serial blood draws, and outcome assessment |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carolina B Maciel, MD, MSCR | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Gainesville | Florida | 32610 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35067230 | Derived | 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. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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: 2250 mg; Crcl< 30 ml/min: 1125 mg) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 3h |
|
|
As per clinical trial protocol, all subjects were monitored daily for adverse (AE) and serious adverse events (SAE) from the time of enrollment for the duration of their ICU stay. The PI monitored patient safety data within 24 hours of AE's or SAE's. The duration of ICU stay for the subjects was approximately 1 week. Screening for visual AE's was planned at the 6-month follow-up visit. Due to inpatient mortality, none of the enrolled subjects completed the 6-month follow-up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open Label | 4500 mg of vigabatrin administered enterally Vigabatrin Only Product: enteral medication administration, serial blood draws, and outcome assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Carolina B. Maciel | University of Florida | (352) 273-5550 | carolina.maciel@ufl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 11, 2023 | Apr 25, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 8, 2021 | Apr 25, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D013226 | Status Epilepticus |
| D003128 | Coma |
| D006323 | Heart Arrest |
| ID | Term |
|---|---|
| D012640 | Seizures |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D020888 | Vigabatrin |
| ID | Term |
|---|---|
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
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pilot feasibility trial of pharmacokinetics of drug absorption
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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.
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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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Creatinine Clearance (CrCl) | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Vigabatrin Dose Administered | Count of Participants | Participants |
|
|
|
| Primary | 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) | Posted | Count of Participants | Participants | 48 hours |
|
|
|
| Primary | 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. | The 6 month follow-up could not be completed for any of the 6 enrolled subjects due to in-hospital mortality | Posted | 6 months |
|
|
| Primary | 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. | 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. | Posted | Count of Participants | Participants | 0h, 72h and 168h following vigabatrin administration |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 0h to 48h after vigabatrin admnistration |
|
|
|
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | 72h and 7 days following vigabatrin administration |
|
|
|
| Secondary | 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). | 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. | Posted | Count of Participants | Participants | Determined at the time of connection to EEG monitoring |
|
|
|
| 6 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D019954 | Neurobehavioral Manifestations |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
|
| Taurine levels collected at 168h |
|
|
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| Undetectable vigabatrin concentration at 7 days |
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| Detectable vigabatrin concentration at 7 days |
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