Efficacy and Safety Study Comparing Lorazepam and Diazepam for Children in the Emergency Department With Seizures (Status 2)

Status Epilepticus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00621478
• Other study ID #: N01HD43393
• Secondary ID: 275200403393C
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 20, 2008
• Last updated: December 14, 2012
• Start date: February 2008
• Est. completion date: May 2012

Study information

• Verified date: July 2012
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 18 Years

Eligibility

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 exclusion criteria may not be known at the time of drug administration due to the need for emergent treatment. Thus patients will be terminated from the study (early terminators) if the investigators discover any of the following conditions after administration of study drug:

1. Pregnancy;

2. Use of a benzodiazepine within 1 week of presentation.

3. Parent/guardian refusal to give informed consent by the methods described;

4. Patient's refusal to assent (for patients = 7 yrs old and mentally competent to understand study procedures) by the methods described, or as required by the local IRB;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Status Epilepticus

Intervention

Drug:
• lorazepam 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.

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
United States	University of Michigan Emergency Medicine Research	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Maryland Hospital for Children	Baltimore	Maryland
United States	Children's Hospital of Buffalo	Buffalo	New York
United States	Children's Medical Center Dallas	Dallas	Texas
United States	University of California- Davis Medical Center	Davis	California
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Medical College of Wisconsin Children's Corporate Center	Milwaukee	Wisconsin
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Utah Pediatric Emergency Medicine	Salt Lake City	Utah
United States	Children's National Medical Center	Washington DC	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	To determine population pharmacokinetics (PK) of lorazepam using sparse sampling.		24 hr	No
Secondary	feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial		2 years	No
Secondary	the experience of community consultation and public disclosure		2 years	No
Secondary	feasibility of enrolling pediatric patients under an exception from informed consent		2 years	No
Secondary	determine patients' and parents' attitudes and reactions to an exception from informed consent approach		2 years	No
Secondary	severe or life-threatening respiratory depression		4 hours	Yes