Status Epilepticus
Conditions
Brief summary
Children with seizures are frequently seen in the emergency department. The drug lorazepam, which is commonly used, is not labeled by the US Food and Drug Administration for children for this use. The FDA, under the Best Pharmaceuticals for Children Act, has requested that a study comparing diazepam, a drug that is labeled by the FDA for this indication, with lorazepam be performed. The study will show whether one drug is more effective and safe than the other.
Detailed description
Textbooks and expert opinion recommend both diazepam and lorazepam as initial therapy for children in status epilepticus (SE) and provide recommended doses that are commonly used. However, unlike diazepam, lorazepam is only FDA-approved for treatment for SE in patients over 18 years of age. Despite this fact, many experts support the use of lorazepam over diazepam in pediatric SE. Increased duration of action, increased effectiveness in terminating SE, and a lower incidence of respiratory depression have been cited as potential advantages of lorazepam over diazepam. However, data to support firm recommendations for one medication over another are lacking. Thus, either diazepam (FDA-approved) or lorazepam can be considered first-line agents for pediatric SE, and the physician's choice of agent depends on local practice patterns and individual treatment styles. In the prehospital (Emergency Medical Services) setting, diazepam is commonly chosen because of a longer shelf life without refrigeration. The purpose of this study is to determine the differences in efficacy and safety between these two commonly used benzodiazepines, as requested by the FDA under the Best Pharmaceuticals for Children Act, using the Exception from Informed Consent provided by the FDA.
Interventions
DRUGlorazepam or diazepam
Administration instructions will ask to deliver 0.04 ml per kilogram of child's weight of the study medication up to a maximum of 1.6 ml. 0.04 ml/kg (maximum dose 1.6 ml) will deliver 0.1 mg/kg of lorazepam (maximum dose 4 mg) and 0.2 mg/kg of diazepam (maximum dose 8 mg). Half of this dose can be repeated in 5 minutes if the patient is still convulsing. The medication will be administered as a slow IV push.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Age 3 months to less than 18 years; 2. Generalized tonic clonic status epilepticus, defined as: 1. Three or more generalized tonic clonic seizures within the last hour and currently experiencing a convulsion (i.e. the current convulsion may be the third convulsion within one hour); or 2. Two or more generalized tonic clonic seizures in succession with no recovery of consciousness between seizures and currently experiencing a convulsion (i.e. the current convulsion may be the second convulsion without recovery of consciousness after the first convulsion); or 3. A seizure that lasts at least 5 minutes that is either generalized tonic clonic in its entirety or starts focal and then generalizes. The seizure must be associated with loss of consciousness
Exclusion criteria
1. Pregnancy; 2. Shock prior to study drug (sustained hypotension requiring inotropic therapy); 3. Significant dysrhythmia prior to study drug (other than sinus tachycardia); 4. Need for emergent surgical intervention and general anesthesia for a condition present prior to study drug; 5. Known sensitivity to benzodiazepines or known contraindication to benzodiazepine use; or 6. Use of a benzodiazepine within 1 week of presentation. Certain
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| cessation of convulsions within 10 minutes of the initial administration of the study drug and a sustained absence of convulsions for 30 minutes from the initial administration of the study drug. | 30 minutes |
Secondary
| Measure | Time frame |
|---|---|
| feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial | 2 years |
| the experience of community consultation and public disclosure | 2 years |
| To determine population pharmacokinetics (PK) of lorazepam using sparse sampling. | 24 hr |
| determine patients' and parents' attitudes and reactions to an exception from informed consent approach | 2 years |
| severe or life-threatening respiratory depression | 4 hours |
| feasibility of enrolling pediatric patients under an exception from informed consent | 2 years |
Countries
Canada, United States
Outcome results
None listed