Benzodiazepine Refractory Status Epilepticus
Conditions
Keywords
status epilepticus, refractory, benzodiazepine, fosphenytoin, levetiracetam, valproic acid
Brief summary
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.
Interventions
Sponsors
University of Michigan
Medical University of South Carolina
Children's National Research Institute
University of Minnesota
National Institute of Neurological Disorders and Stroke (NINDS)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | Within 60 minutes after the start of study drug infusion | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat |
| Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | Within 60 minutes after the start of study drug infusion | Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis |
| Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | Within 60 minutes after the start of study drug infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | within 20 minutes | 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. |
| Number of Participants With Admission to Intensive Care Unit | Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient | ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient. |
| Length of Hospital Stay | length of hospital stay | Length of hospital stay in days |
| Length of ICU Stay | number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study | 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. |
| Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | start of drug infusion to seizure cessation | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Safety Outcome: Life Threatening Hypotension | within 60 minutes of the start of study drug infusion | Life-threatening hypotension within 60 minutes of the start of study drug infusion |
| Number of Participants With Safety Outcome: Acute Seizure Recurrence | 60 minutes to 12 hours after start of study drug infusion | acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion |
| Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | within 60 minutes of the start of study drug infusion | Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion |
| Number of Participants With Safety Outcome: Endotracheal Intubation | within 60 minutes of start of study drug infusion | Endotracheal intubation within 60 minutes of start of study drug infusion |
| Number of Participants With Safety Outcome: Acute Anaphylaxis | within 6 hours of the start of study drug infusions | 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. |
| Number of Participants With Safety Outcome: Acute Respiratory Depression | 24 hours | 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. |
| Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | 24 hours | Safety outcome: Hepatic transaminase or ammonia elevations |
| Number of Participants With Safety Outcome: Purple Glove Syndrome | 24 hours | 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. |
| Number of Participants With Safety Outcome: Death | 30 days | Safety outcome: Death |
Countries
United States
Participant flow
Recruitment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 118 |
| 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 | 121 |
| 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 | 145 |
| Total | 384 |
Baseline characteristics
| Characteristic | Total | Fosphenytoin (FOS) | Valproic Acid | Levetiracetam |
|---|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 25.6 | 32.8 years STANDARD_DEVIATION 25.4 | 32.2 years STANDARD_DEVIATION 25.4 | 33.3 years STANDARD_DEVIATION 26 |
| Age, Customized Age 0 - 5 yr | 82 Participants | 24 Participants | 28 Participants | 30 Participants |
| Age, Customized Age 11 - 20 yr | 37 Participants | 10 Participants | 18 Participants | 9 Participants |
| Age, Customized Age 21 - 40 yr | 70 Participants | 20 Participants | 19 Participants | 31 Participants |
| Age, Customized Age 41 - 60 yr | 86 Participants | 26 Participants | 26 Participants | 34 Participants |
| Age, Customized Age 6 - 10 yr | 39 Participants | 15 Participants | 7 Participants | 17 Participants |
| Age, Customized Age => 61 yr | 70 Participants | 23 Participants | 23 Participants | 24 Participants |
| Final Diagnosis Non-epileptic spell | 37 Participants | 11 Participants | 13 Participants | 13 Participants |
| Final Diagnosis Seizure/Status Epilepticus | 334 Participants | 104 Participants | 102 Participants | 128 Participants |
| Final Diagnosis Unable to adjudicate | 13 Participants | 3 Participants | 6 Participants | 4 Participants |
| Prior history of epilepsy | 260 Participants | 80 Participants | 83 Participants | 97 Participants |
| Race/Ethnicity, Customized Hispanic Ethnicity | 63 Participants | 18 Participants | 22 Participants | 23 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black | 165 Participants | 49 Participants | 54 Participants | 62 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other, >1 race, or unknown | 59 Participants | 20 Participants | 18 Participants | 21 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 160 Participants | 49 Participants | 49 Participants | 62 Participants |
| Sex: Female, Male Female | 171 Participants | 47 Participants | 56 Participants | 68 Participants |
| Sex: Female, Male Male | 213 Participants | 71 Participants | 65 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 125 | 2 / 125 | 7 / 150 |
| other Total, other adverse events | 28 / 125 | 22 / 125 | 25 / 150 |
| serious Total, serious adverse events | 57 / 125 | 46 / 125 | 64 / 150 |
Outcome results
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.
Time frame: Within 60 minutes after the start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | 57 Participants |
| Valproic Acid | Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | 60 Participants |
| Levetiracetam | Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis | 67 Participants |
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
Time frame: Within 60 minutes after the start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | 53 Participants |
| Valproic Acid | Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | 56 Participants |
| Levetiracetam | Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat | 68 Participants |
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
Time frame: Within 60 minutes after the start of study drug infusion
Population: The analysis population for this outcome is the Per-protocol population, which is all patients who completed the study without major protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | 37 Participants |
| Valproic Acid | Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | 43 Participants |
| Levetiracetam | Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis | 51 Participants |
Secondary
Length of Hospital Stay
Length of hospital stay in days
Time frame: length of hospital stay
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fosphenytoin (FOS) | Length of Hospital Stay | 3 days |
| Valproic Acid | Length of Hospital Stay | 3 days |
| Levetiracetam | Length of Hospital Stay | 3 days |
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.
Time frame: number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fosphenytoin (FOS) | Length of ICU Stay | 1 days |
| Valproic Acid | Length of ICU Stay | 1 days |
| Levetiracetam | Length of ICU Stay | 1 days |
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.
Time frame: start of drug infusion to seizure cessation
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fosphenytoin (FOS) | Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | 11.7 minutes |
| Valproic Acid | Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | 7.0 minutes |
| Levetiracetam | Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success | 10.5 minutes |
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.
Time frame: Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Admission to Intensive Care Unit | 70 Participants |
| Valproic Acid | Number of Participants With Admission to Intensive Care Unit | 71 Participants |
| Levetiracetam | Number of Participants With Admission to Intensive Care Unit | 87 Participants |
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.
Time frame: within 20 minutes
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | 43 Participants |
| Valproic Acid | Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | 43 Participants |
| Levetiracetam | Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success | 53 Participants |
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.
Time frame: within 6 hours of the start of study drug infusions
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Acute Anaphylaxis | 0 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Acute Anaphylaxis | 0 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Acute Anaphylaxis | 0 Participants |
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.
Time frame: 24 hours
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Acute Respiratory Depression | 16 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Acute Respiratory Depression | 10 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Acute Respiratory Depression | 12 Participants |
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
Time frame: 60 minutes to 12 hours after start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Acute Seizure Recurrence | 14 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Acute Seizure Recurrence | 14 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Acute Seizure Recurrence | 16 Participants |
Other Pre-specified
Number of Participants With Safety Outcome: Death
Safety outcome: Death
Time frame: 30 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Death | 3 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Death | 2 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Death | 7 Participants |
Other Pre-specified
Number of Participants With Safety Outcome: Endotracheal Intubation
Endotracheal intubation within 60 minutes of start of study drug infusion
Time frame: within 60 minutes of start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Endotracheal Intubation | 33 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Endotracheal Intubation | 21 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Endotracheal Intubation | 30 Participants |
Other Pre-specified
Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations
Safety outcome: Hepatic transaminase or ammonia elevations
Time frame: 24 hours
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | 0 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | 1 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations | 1 Participants |
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
Time frame: within 60 minutes of the start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | 0 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | 0 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia | 1 Participants |
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
Time frame: within 60 minutes of the start of study drug infusion
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Life Threatening Hypotension | 4 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Life Threatening Hypotension | 2 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Life Threatening Hypotension | 1 Participants |
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.
Time frame: 24 hours
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fosphenytoin (FOS) | Number of Participants With Safety Outcome: Purple Glove Syndrome | 0 Participants |
| Valproic Acid | Number of Participants With Safety Outcome: Purple Glove Syndrome | 0 Participants |
| Levetiracetam | Number of Participants With Safety Outcome: Purple Glove Syndrome | 0 Participants |