Efficacy and Safety Study Comparing Lorazepam and Diazepam for Children in the Emergency Department With Seizures

Condition(s) targeted: Status Epilepticus

Intervention: lorazepam or diazepam (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
James Chamberlain, MD, Principal Investigator, Affiliation: Children's Research Institute

Overall contact:
James Chamberlain, MD, Phone: 202-476-3253, Email: jchamber@cnmc.org

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.

Official title: Use Of Lorazepam For The Treatment Of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial Of Lorazepam And Diazepam

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome:

To determine population pharmacokinetics (PK) of lorazepam using sparse sampling.

feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial

the experience of community consultation and public disclosure

feasibility of enrolling pediatric patients under an exception from informed consent

determine patients' and parents' attitudes and reactions to an exception from informed consent approach

severe or life-threatening respiratory depression

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.

Minimum age: 3 Months. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Generalized tonic-clonic status epilepticus, defined as one or more if the following:

1. Three or more generalized tonic-clonic seizures within the last hour and currently experiencing a convulsion; or

2. Two or more generalized tonic-clonic seizures in succession with no recovery of consciousness between seizures and currently experiencing a convulsion; or

3. A single ongoing generalized tonic-clonic seizure of at least 5 minutes duration

Exclusion Criteria:

Pregnancy Shock prior to study drug (sustained hypotension requiring inotropic therapy); Significant dysrhythmia prior to study drug (other than sinus tachycardia); Need for emergent surgical intervention and general anesthesia for a condition present prior to study drug; Known sensitivity to benzodiazepines or known contraindication to benzodiazepine use; or Use of diazepam or lorazepam within 1 week of presentation.

James Chamberlain, MD, Phone: 202-476-3253, Email: jchamber@cnmc.org

Children's National Medical Center, Washington DC, District of Columbia 20010, United States; Recruiting
Jim Chamberlain, MD, Phone: 202-476-3253, Email: jchamber@cnmc.org

Starting date: February 2008
Ending date: January 2011
Last updated: May 26, 2009