Benzodiazepine Refractory Status Epilepticus Clinical Trial
— ESETTOfficial title:
A Multicenter, Randomized, Blinded, Comparative Effectiveness Study of Fosphenytoin, Valproic Acid, or Levetiracetam in the Emergency Department Treatment of Patients With Benzodiazepine-refractory Status Epilepticus.
| Verified date | May 2021 |
| Source | University of Virginia |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 478 |
| Est. completion date | May 2019 |
| Est. primary completion date | February 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | C.S. Mott Children's Hospital | Ann Arbor | Michigan |
| United States | University of Michigan Medical Center | Ann Arbor | Michigan |
| United States | Children's Healthcare of Atlanta at Egleston | Atlanta | Georgia |
| United States | Grady Memorial Hospital | Atlanta | Georgia |
| United States | University of maryland Medical Center | Baltimore | Maryland |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Kings County Hospital Center | Brooklyn | New York |
| United States | Maimonides Medical Center | Brooklyn | New York |
| United States | SUNY Downstate Medical Center | Brooklyn | New York |
| United States | University of Virginia | Charlottesville | Virginia |
| United States | Crozer-Chester Medical Center | Chester | Pennsylvania |
| United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
| United States | University of Cincinnati Medical Center | Cincinnati | Ohio |
| United States | Nationwide Children's Hospital | Columbus | Ohio |
| United States | OSU Wexner Medical Center | Columbus | Ohio |
| United States | Children's Medical Center UTSW | Dallas | Texas |
| United States | Children's Hospital of Michigan | Detroit | Michigan |
| United States | Detroit Receiving Hospital | Detroit | Michigan |
| United States | Henry Ford Hospital | Detroit | Michigan |
| United States | Sinai-Grace Hospital | Detroit | Michigan |
| United States | Fairview Southdale Hospital | Edina | Minnesota |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | Penn State Hershey Medical Center | Hershey | Pennsylvania |
| United States | Lyndon B. Johnson General Hospital | Houston | Texas |
| United States | Memorial Hermann Texas medical Center | Houston | Texas |
| United States | Texas Children's Hospital | Houston | Texas |
| United States | University of Kentucky Hospital | Lexington | Kentucky |
| United States | Ronald Reagan UCLA Medical Center | Los Angeles | California |
| United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
| United States | Froedtert Memorial Lutheran Hospital | Milwaukee | Wisconsin |
| United States | Hennepin County Medical Center | Minneapolis | Minnesota |
| United States | University of Minnesota Masonic Children's Hospital | Minneapolis | Minnesota |
| United States | University of Minnesota Medical Center | Minneapolis | Minnesota |
| United States | NYP Columbia University Medical Center | New York | New York |
| United States | NYP Morgan Stanley Children's Hospital | New York | New York |
| United States | Christiana Hospital | Newark | Delaware |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | Einstein Medical Center | Philadelphia | Pennsylvania |
| United States | Hahnemann University Hospital | Philadelphia | Pennsylvania |
| United States | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Penn Presbyterian Medical Center | Philadelphia | Pennsylvania |
| United States | Pennsylvania Hospital | Philadelphia | Pennsylvania |
| United States | Temple University Hospital | Philadelphia | Pennsylvania |
| United States | Temple University Hospital Episcopal Campus | Philadelphia | Pennsylvania |
| United States | Allegheny General Hospital | Pittsburgh | Pennsylvania |
| United States | Children's Hospital of Pittsburgh UPMC | Pittsburgh | Pennsylvania |
| United States | UPMC Mercy Hospital | Pittsburgh | Pennsylvania |
| United States | UPMC Presbyterian Hospital | Pittsburgh | Pennsylvania |
| United States | Oregon Health & Science University Hospital | Portland | Oregon |
| United States | Hasbro Children's Hospital | Providence | Rhode Island |
| United States | Rhode Island Hospital | Providence | Rhode Island |
| United States | VCU Medical Center | Richmond | Virginia |
| United States | UC Davis Children's Hospital | Sacramento | California |
| United States | St. Louis Children's Hospital | Saint Louis | Missouri |
| United States | Regions Hospital | Saint Paul | Minnesota |
| United States | Primary Children's Hospital | Salt Lake City | Utah |
| United States | University Health System University Hospital | San Antonio | Texas |
| United States | San Francisco General Hospital | San Francisco | California |
| United States | UCSF Benioff Children's Hospital | San Francisco | California |
| United States | UCSF Medical Center | San Francisco | California |
| United States | Stanford University Medical Center | Stanford | California |
| United States | Banner University Medical Center - South Campus | Tucson | Arizona |
| United States | Banner University Medical Center-Tucson Campus | Tucson | Arizona |
| United States | Children's National Medical Center | Washington | District of Columbia |
| United States | A.I.DuPont Hospital for Children | Wilmington | Delaware |
| Lead Sponsor | Collaborator |
|---|---|
| University of Virginia | Children's National Research Institute, Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), University of Michigan, University of Minnesota |
United States,
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 6:89-92. doi: 10.1111/epi.12288. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | 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 | |
| Other | Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion | within 60 minutes of the start of study drug infusion | |
| Other | 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 | |
| Other | 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 | |
| Other | 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 | |
| Other | Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | Safety outcome: Hepatic transaminase or ammonia elevations | 24 hours | |
| Other | 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 | |
| Other | Number of Participants With Safety Outcome: Death | Safety outcome: Death | 30 days | |
| Other | 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 | |
| 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 | 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 | 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. | 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. | 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. | 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. | 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. | within 20 minutes | |
| Secondary | Length of Hospital Stay | Length of hospital stay in days | length of hospital stay |