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| ID | Type | Description | Link |
|---|---|---|---|
| 119756 | Other Identifier | ClinicalTrials.gov | |
| U01NS088034 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Michigan | OTHER |
| Medical University of South Carolina | OTHER |
| Children's National Research Institute | OTHER |
| University of Minnesota |
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The primary objective is to determine the most effective and/or the least effective treatment of benzodiazepine-refractory status epilepticus (SE) among patients older than 2 years. There are three active treatment arms being compared: fosphenytoin (FOS),levetiracetam (LEV), and valproic acid (VPA).
The second objective is comparison of three drugs with respect to secondary outcomes.
The final objective is to ensure that the trial is informative for treatment of established SE in children by describing the effectiveness, safety, and rate of adverse reactions of these drugs in children.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fosphenytoin (FOS) | Active Comparator | Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. |
|
| Valproic acid | Active Comparator | Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. |
|
| Levetiracetam | Active Comparator | Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fosphenytoin | Drug |
| ||
| Levetiracetam |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat | Within 60 minutes after the start of study drug infusion |
| Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis | Within 60 minutes after the start of study drug infusion |
| Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review. | Within 60 minutes after the start of study drug infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Admission to Intensive Care Unit | ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient. | Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient |
| Length of ICU Stay |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Safety Outcome: Life Threatening Hypotension | Life-threatening hypotension within 60 minutes of the start of study drug infusion | within 60 minutes of the start of study drug infusion |
| Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia |
Inclusion Criteria: Patient witnessed to seize for greater than 5 minute duration prior to treatment with study drug; Patient received adequate dose of benzodiazepines. The last dose of a benzo was administered in the 5-30 minutes prior to study drug administration. The doses may be divided.; continued or recurring seizure in the Emergency Department; Age 2 years or older
Exclusion Criteria:Known pregnancy; Prisoner; Opt-out identification; Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital or other agents defined in the MoP) for this episode of SE; Treatment with sedatives with anticonvulsant properties other than benzodiazepines (propofol, etomidate, ketamine or other agents defined in the MoP); Endotracheal intubation; Acute traumatic brain injury; Known metabolic disorder; Known liver disease; Known severe renal impairment; Known allergy or other known contraindication to FOS, PHT, LEV, or VPA; Hypoglycemia < 50 mg/dL; Hyperglycemia > 400 mg/dL; Cardiac arrest and post-anoxic seizures
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| Name | Affiliation | Role |
|---|---|---|
| Jaideep Kapur, MBBS, PhD | University of Virginia | Study Chair |
| Robert Silbergleit, MD | University of Michigan | Principal Investigator |
| James Chamberlain, MD | Children's National Research Institute | Principal Investigator |
| Jordan Elm, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner University Medical Center - South Campus | Tucson | Arizona | 85713 | United States | ||
| Banner University Medical Center-Tucson Campus |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24001084 | Background | Bleck T, Cock H, Chamberlain J, Cloyd J, Connor J, Elm J, Fountain N, Jones E, Lowenstein D, Shinnar S, Silbergleit R, Treiman D, Trinka E, Kapur J. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6(0 6):89-92. doi: 10.1111/epi.12288. | |
| 21967363 | Background | Cock HR; ESETT Group. Established status epilepticus treatment trial (ESETT). Epilepsia. 2011 Oct;52 Suppl 8:50-2. doi: 10.1111/j.1528-1167.2011.03237.x. |
| Label | URL |
|---|---|
| ESETT Website | View source |
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ESETT had a total of 478 enrollments. This number includes 16 re-enrollers. This was an EFIC trial so all consents happened after treatment. All enrollments went through the same process of consent even if they were reenrolled. The first 400 patients were used in several parts of analyses since the trial stopped early for futility (prespecified).
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| ID | Title | Description |
|---|---|---|
| FG000 | Fosphenytoin (FOS) | Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin |
| FG001 | Valproic Acid |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Dec 5, 2016 |
Not provided
| OTHER |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
ESETT had 478 enrollments. They were 16 re-enrollers. This was an EFIC trial so all consents happened after treatment and all enrollments went through the same process of consent even if they were re-enrolled. Some information presented here only includes the first 400 patients since there was a prespecified stopping rule and the trial stopped early for futility.
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|
| Valproic acid | Drug |
|
Length of stay is determined by the number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study. |
| number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study |
| Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | The time to termination of seizures is the interval from the start of study drug infusion to cessation of clinically apparent seizure in those who meet the primary outcome. | start of drug infusion to seizure cessation |
| Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | Number of participants with seizure cessation within 20 minutes of study drug initiation for patients with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper. | within 20 minutes |
| Length of Hospital Stay | Length of hospital stay in days | length of hospital stay |
Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion |
| within 60 minutes of the start of study drug infusion |
| Number of Participants With Safety Outcome: Endotracheal Intubation | Endotracheal intubation within 60 minutes of start of study drug infusion | within 60 minutes of start of study drug infusion |
| Number of Participants With Safety Outcome: Acute Anaphylaxis | Acute anaphylaxis is defined as a clinical presentation consistent with life threatening allergic reaction occurring within 6 hours of the start of study drug infusions and manifested as urticaria in combination with either (1) a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes, or (2) objective evidence of airway obstruction, and for which the patient was treated with antihistamines and/or steroids. | within 6 hours of the start of study drug infusions |
| Number of Participants With Safety Outcome: Acute Respiratory Depression | Respiratory depression is defined as impairment of ventilation or oxygenation necessitating definitive endotracheal intubation and mechanical ventilation. It is distinct from intubations performed only for airway protection in those with decreased levels of consciousness. It does not include those getting only supraglottic airways or transient bag-valve-mask support. | 24 hours |
| Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | Safety outcome: Hepatic transaminase or ammonia elevations | 24 hours |
| Number of Participants With Safety Outcome: Purple Glove Syndrome | Purple glove syndrome is defined as the presence of all three of the findings of the objective edema: discoloration, and pain in the distal extremity in which study drug was administered, with or without known extravasation, and for which there is no other evident etiology. | 24 hours |
| Number of Participants With Safety Outcome: Death | Safety outcome: Death | 30 days |
| Number of Participants With Safety Outcome: Acute Seizure Recurrence | acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion | 60 minutes to 12 hours after start of study drug infusion |
| Tucson |
| Arizona |
| 85724 |
| United States |
| Ronald Reagan UCLA Medical Center | Los Angeles | California | 90095 | United States |
| UC Davis Children's Hospital | Sacramento | California | 95817 | United States |
| San Francisco General Hospital | San Francisco | California | 94110 | United States |
| UCSF Medical Center | San Francisco | California | 94143 | United States |
| UCSF Benioff Children's Hospital | San Francisco | California | 94145 | United States |
| Stanford University Medical Center | Stanford | California | 94305 | United States |
| Christiana Hospital | Newark | Delaware | 19718 | United States |
| A.I.DuPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20310 | United States |
| Grady Memorial Hospital | Atlanta | Georgia | 30303 | United States |
| Children's Healthcare of Atlanta at Egleston | Atlanta | Georgia | 30322 | United States |
| University of Kentucky Hospital | Lexington | Kentucky | 40536 | United States |
| University of maryland Medical Center | Baltimore | Maryland | 21201 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| C.S. Mott Children's Hospital | Ann Arbor | Michigan | 48109 | United States |
| University of Michigan Medical Center | Ann Arbor | Michigan | 48109 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| Detroit Receiving Hospital | Detroit | Michigan | 48201 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Sinai-Grace Hospital | Detroit | Michigan | 48235 | United States |
| Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| University of Minnesota Medical Center | Minneapolis | Minnesota | 55454 | United States |
| University of Minnesota Masonic Children's Hospital | Minneapolis | Minnesota | 55455 | United States |
| Regions Hospital | Saint Paul | Minnesota | 55101 | United States |
| St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Kings County Hospital Center | Brooklyn | New York | 11203 | United States |
| SUNY Downstate Medical Center | Brooklyn | New York | 11203 | United States |
| Maimonides Medical Center | Brooklyn | New York | 11219 | United States |
| NYP Columbia University Medical Center | New York | New York | 10032 | United States |
| NYP Morgan Stanley Children's Hospital | New York | New York | 10032 | United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45219 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| OSU Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| Oregon Health & Science University Hospital | Portland | Oregon | 97239 | United States |
| Crozer-Chester Medical Center | Chester | Pennsylvania | 19013 | United States |
| Penn State Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| Hahnemann University Hospital | Philadelphia | Pennsylvania | 19102 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Penn Presbyterian Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
| Pennsylvania Hospital | Philadelphia | Pennsylvania | 19107 | United States |
| Temple University Hospital Episcopal Campus | Philadelphia | Pennsylvania | 19125 | United States |
| Temple University Hospital | Philadelphia | Pennsylvania | 19140 | United States |
| Einstein Medical Center | Philadelphia | Pennsylvania | 19141 | United States |
| Allegheny General Hospital | Pittsburgh | Pennsylvania | 15212 | United States |
| UPMC Presbyterian Hospital | Pittsburgh | Pennsylvania | 15213 | United States |
| UPMC Mercy Hospital | Pittsburgh | Pennsylvania | 15219 | United States |
| Children's Hospital of Pittsburgh UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Hasbro Children's Hospital | Providence | Rhode Island | 02903 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| Children's Medical Center UTSW | Dallas | Texas | 75390 | United States |
| Lyndon B. Johnson General Hospital | Houston | Texas | 77026 | United States |
| Memorial Hermann Texas medical Center | Houston | Texas | 77030 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| University Health System University Hospital | San Antonio | Texas | 78229 | United States |
| Primary Children's Hospital | Salt Lake City | Utah | 84113 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| VCU Medical Center | Richmond | Virginia | 23298 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Froedtert Memorial Lutheran Hospital | Milwaukee | Wisconsin | 53226 | United States |
| 35718575 | Derived | Coralic Z, Kapur J, Olson KR, Chamberlain JM, Overbeek D, Silbergleit R. Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med. 2022 Sep;80(3):194-202. doi: 10.1016/j.annemergmed.2022.04.020. Epub 2022 Jun 17. |
| 34032604 | Derived | Rosenthal ES, Elm JJ, Ingles J, Rogers AJ, Terndrup TE, Holsti M, Thomas DG, Babcock L, Okada PJ, Lipsky RH, Miller JB, Hickey RW, Barra ME, Bleck TP, Cloyd JC, Silbergleit R, Lowenstein DH, Coles LD, Kapur J, Shinnar S, Chamberlain JM; Established Status Epilepticus Treatment Trial Study Group. Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus. Neurology. 2021 May 11;96(19):e2372-e2386. doi: 10.1212/WNL.0000000000011879. Epub 2021 Mar 23. |
| 33742783 | Derived | Sathe AG, Brundage RC, Ivaturi V, Cloyd JC, Chamberlain JM, Elm JJ, Silbergleit R, Kapur J, Coles LD. A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure. Clin Transl Sci. 2021 Jul;14(4):1444-1451. doi: 10.1111/cts.13004. Epub 2021 May 1. |
| 33567109 | Derived | Sathe AG, Underwood E, Coles LD, Elm JJ, Silbergleit R, Chamberlain JM, Kapur J, Cock HR, Fountain NB, Shinnar S, Lowenstein DH, Rosenthal ES, Conwit RA, Bleck TP, Cloyd JC. Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial. Epilepsia. 2021 Mar;62(3):795-806. doi: 10.1111/epi.16825. Epub 2021 Feb 10. |
| 33336359 | Derived | Sathe AG, Mishra U, Ivaturi V, Brundage RC, Cloyd JC, Elm JJ, Chamberlain JM, Silbergleit R, Kapur J, Lowenstein DH, Shinnar S, Cock HR, Fountain NB, Babcock L, Coles LD. Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus. J Clin Pharmacol. 2021 Jun;61(6):763-768. doi: 10.1002/jcph.1801. Epub 2021 Jan 12. |
| 32446674 | Derived | Scicluna VM, Biros M, Harney DK, Jones EB, Mitchell AR, Pentz RD, Silbergleit R, Speight CD, Wright DW, Dickert NW. Patient and Surrogate Postenrollment Perspectives on Research Using the Exception From Informed Consent: An Integrated Survey. Ann Emerg Med. 2020 Sep;76(3):343-349. doi: 10.1016/j.annemergmed.2020.03.017. Epub 2020 May 21. |
| 32203691 | Derived | Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, Rogers A, Barsan W, Cloyd J, Lowenstein D, Bleck TP, Conwit R, Meinzer C, Cock H, Fountain NB, Underwood E, Connor JT, Silbergleit R; Neurological Emergencies Treatment Trials; Pediatric Emergency Care Applied Research Network investigators. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020 Apr 11;395(10231):1217-1224. doi: 10.1016/S0140-6736(20)30611-5. Epub 2020 Mar 20. |
| 31774955 | Derived | Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. |
| 31161706 | Derived | Sathe AG, Tillman H, Coles LD, Elm JJ, Silbergleit R, Chamberlain J, Kapur J, Cock HR, Fountain NB, Shinnar S, Lowenstein DH, Conwit RA, Bleck TP, Cloyd JC. Underdosing of Benzodiazepines in Patients With Status Epilepticus Enrolled in Established Status Epilepticus Treatment Trial. Acad Emerg Med. 2019 Aug;26(8):940-943. doi: 10.1111/acem.13811. Epub 2019 Jul 18. No abstract available. |
Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid |
| FG002 | Levetiracetam | Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam |
| COMPLETED |
|
| NOT COMPLETED |
|
The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study, and the first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Fosphenytoin (FOS) | Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin |
| BG001 | Valproic Acid | Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid |
| BG002 | Levetiracetam | Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Prior history of epilepsy | Count of Participants | Participants |
| ||||||||||||||||
| Final Diagnosis | Count of Participants | Participants |
|
| 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 | Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat | The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | Within 60 minutes after the start of study drug infusion |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis | The analysis population for this outcome is the Per-protocol population, which is all patients who completed the study without major protocol deviations. | Posted | Count of Participants | Participants | Within 60 minutes after the start of study drug infusion |
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review. | The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | Within 60 minutes after the start of study drug infusion |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Admission to Intensive Care Unit | ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient. | The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient |
| ||||||||||||||||||||||||||||||||||
| Secondary | Length of ICU Stay | Length of stay is determined by the number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study. | The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Median | Inter-Quartile Range | days | number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study |
| |||||||||||||||||||||||||||||||||
| Secondary | Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | The time to termination of seizures is the interval from the start of study drug infusion to cessation of clinically apparent seizure in those who meet the primary outcome. | The analysis population here is different than Participant Flow because it includes only the patients who had this data available. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Median | Inter-Quartile Range | minutes | start of drug infusion to seizure cessation |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | Number of participants with seizure cessation within 20 minutes of study drug initiation for patients with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper. | The population is different than Participant flow because it is only those with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper. | Posted | Count of Participants | Participants | within 20 minutes |
| ||||||||||||||||||||||||||||||||||
| Secondary | Length of Hospital Stay | Length of hospital stay in days | The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Median | Inter-Quartile Range | days | length of hospital stay |
| |||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Life Threatening Hypotension | Life-threatening hypotension within 60 minutes of the start of study drug infusion | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | within 60 minutes of the start of study drug infusion |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | within 60 minutes of the start of study drug infusion |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Endotracheal Intubation | Endotracheal intubation within 60 minutes of start of study drug infusion | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | within 60 minutes of start of study drug infusion |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Acute Anaphylaxis | Acute anaphylaxis is defined as a clinical presentation consistent with life threatening allergic reaction occurring within 6 hours of the start of study drug infusions and manifested as urticaria in combination with either (1) a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes, or (2) objective evidence of airway obstruction, and for which the patient was treated with antihistamines and/or steroids. | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | within 6 hours of the start of study drug infusions |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Acute Respiratory Depression | Respiratory depression is defined as impairment of ventilation or oxygenation necessitating definitive endotracheal intubation and mechanical ventilation. It is distinct from intubations performed only for airway protection in those with decreased levels of consciousness. It does not include those getting only supraglottic airways or transient bag-valve-mask support. | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | 24 hours |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | Safety outcome: Hepatic transaminase or ammonia elevations | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | 24 hours |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Purple Glove Syndrome | Purple glove syndrome is defined as the presence of all three of the findings of the objective edema: discoloration, and pain in the distal extremity in which study drug was administered, with or without known extravasation, and for which there is no other evident etiology. | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | 24 hours |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Death | Safety outcome: Death | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | 30 days |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Safety Outcome: Acute Seizure Recurrence | acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion | The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility. | Posted | Count of Participants | Participants | 60 minutes to 12 hours after start of study drug infusion |
|
Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial.
All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fosphenytoin (FOS) | Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin | 3 | 125 | 57 | 125 | 28 | 125 |
| EG001 | Valproic Acid | Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid | 2 | 125 | 46 | 125 | 22 | 125 |
| EG002 | Levetiracetam | Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam | 7 | 150 | 64 | 150 | 25 | 150 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental overdose | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Agitation | Psychiatric disorders | Non-systematic Assessment |
| ||
| Aspiration | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
| ||
| Bacteraemia | Infections and infestations | Non-systematic Assessment |
| ||
| Cardiac arrest | Cardiac disorders | Non-systematic Assessment |
| ||
| Cerebral infarction | Nervous system disorders | Non-systematic Assessment |
| ||
| Cerebrovascular accident | Nervous system disorders | Non-systematic Assessment |
| ||
| Cerebrovascular spasm | Nervous system disorders | Non-systematic Assessment |
| ||
| Clostridium difficile colitis | Infections and infestations | Non-systematic Assessment |
| ||
| Conversion disorder | Psychiatric disorders | Non-systematic Assessment |
| ||
| Convulsion | Nervous system disorders | Non-systematic Assessment |
| ||
| Deep vein thrombosis | Vascular disorders | Non-systematic Assessment |
| ||
| Delirium | Psychiatric disorders | Non-systematic Assessment |
| ||
| Depressed level of consciousness | Nervous system disorders | Non-systematic Assessment |
| ||
| Device malfunction | General disorders | Non-systematic Assessment |
| ||
| Dysphagia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Non-systematic Assessment |
| ||
| Endocarditis | Infections and infestations | Non-systematic Assessment |
| ||
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Gastrointestinal haemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Haemorrhage intracranial | Nervous system disorders | Non-systematic Assessment |
| ||
| Hepatic failure | Hepatobiliary disorders | Non-systematic Assessment |
| ||
| Hypoglycaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypokalaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypotension | Vascular disorders | Non-systematic Assessment |
| ||
| Hypothermia | General disorders | Non-systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Hypoxic-ischaemic encephalopathy | Nervous system disorders | Non-systematic Assessment |
| ||
| Infusion site extravasation | General disorders | Non-systematic Assessment |
| ||
| Intestinal ischaemia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Intracardiac thrombus | Cardiac disorders | Non-systematic Assessment |
| ||
| Liver function test abnormal | Investigations | Non-systematic Assessment |
| ||
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Non-systematic Assessment |
| ||
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Respiratory tract infection | Infections and infestations | Non-systematic Assessment |
| ||
| Retroperitoneal haemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Sepsis | Infections and infestations | Non-systematic Assessment |
| ||
| Septic shock | Infections and infestations | Non-systematic Assessment |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Stridor | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Supraventricular tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| Urinary retention | Renal and urinary disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Agitation | Psychiatric disorders | Non-systematic Assessment |
| ||
| Apnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Arrhythmia | Cardiac disorders | Non-systematic Assessment |
| ||
| Atelectasis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Balance disorder | Nervous system disorders | Non-systematic Assessment |
| ||
| Conversion disorder | Psychiatric disorders | Non-systematic Assessment |
| ||
| Convulsion | Nervous system disorders | Non-systematic Assessment |
| ||
| Deep vein thrombosis | Vascular disorders | Non-systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Haematuria | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Headache | Nervous system disorders | Non-systematic Assessment |
| ||
| Heart rate decreased | Investigations | Non-systematic Assessment |
| ||
| Hemiparesis | Nervous system disorders | Non-systematic Assessment |
| ||
| Hypernatraemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hyperphosphataemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypersensitivity | Immune system disorders | Non-systematic Assessment |
| ||
| Hyperthermia | General disorders | Non-systematic Assessment |
| ||
| Hypocalcaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypoglycaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypokalaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypomagnesaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypophosphataemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypotension | Vascular disorders | Non-systematic Assessment |
| ||
| Infusion site extravasation | General disorders | Non-systematic Assessment |
| ||
| Leukocytosis | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Mediastinal haemorrhage | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Neck pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Pancreatitis | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Partial seizures | Nervous system disorders | Non-systematic Assessment |
| ||
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Postictal paralysis | Nervous system disorders | Non-systematic Assessment |
| ||
| Pruritus | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Pyrexia | General disorders | Non-systematic Assessment |
| ||
| Respiratory acidosis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Somnolence | Nervous system disorders | Non-systematic Assessment |
| ||
| Status epilepticus | Nervous system disorders | Non-systematic Assessment |
| ||
| Systemic inflammatory response syndrome | General disorders | Non-systematic Assessment |
| ||
| Tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| Troponin increased | Investigations | Non-systematic Assessment |
| ||
| Upper airway obstruction | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jordan Elm, PhD Biostatistician | Medical University of South Carolina | 843-876-1605 | elmj@musc.edu |
| Dec 30, 2019 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 5, 2015 | May 19, 2021 | ICF_001.pdf |
| ID | Term |
|---|---|
| D013226 | Status Epilepticus |
| ID | Term |
|---|---|
| D012640 | Seizures |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C043114 | fosphenytoin |
| D000077287 | Levetiracetam |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
Not provided
Not provided
| 6 - 10 yr |
|
| 11 - 20 yr |
|
| 21 - 40 yr |
|
| 41 - 60 yr |
|
| => 61 yr |
|
| Male |
|
| White |
|
| Other, >1 race, or unknown |
|
| Non-epileptic spell |
|
| Unable to adjudicate |
|
|
|
| OG002 | Levetiracetam | Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam |
|
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|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
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|
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|
Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam |
|
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|
| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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