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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionStatus Epilepticus
InterventionDrug: lorazepam or diazepam
PhasePhase 2/Phase 3
SponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible PartyEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov IdentifierNCT00621478
First ReceivedFebruary 20, 2008
Last UpdatedDecember 14, 2012
Last verifiedJuly 2012

Tracking Information[ + expand ][ + ]

First Received DateFebruary 20, 2008
Last Updated DateDecember 14, 2012
Start DateFebruary 2008
Estimated Primary Completion DateMay 2012
Current Primary Outcome Measurescessation 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. [Time Frame: 30 minutes] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • To determine population pharmacokinetics (PK) of lorazepam using sparse sampling. [Time Frame: 24 hr] [Designated as safety issue: No]
  • feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial [Time Frame: 2 years] [Designated as safety issue: No]
  • the experience of community consultation and public disclosure [Time Frame: 2 years] [Designated as safety issue: No]
  • feasibility of enrolling pediatric patients under an exception from informed consent [Time Frame: 2 years] [Designated as safety issue: No]
  • determine patients' and parents' attitudes and reactions to an exception from informed consent approach [Time Frame: 2 years] [Designated as safety issue: No]
  • severe or life-threatening respiratory depression [Time Frame: 4 hours] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy and Safety Study Comparing Lorazepam and Diazepam for Children in the Emergency Department With Seizures (Status 2)
Official TitleUse Of Lorazepam For The Treatment Of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial Of Lorazepam And Diazepam
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.
Study TypeInterventional
Study PhasePhase 2/Phase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
ConditionStatus Epilepticus
InterventionDrug: 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.
Other Names:
  • Ativan
  • Valium
Study Arm (s)
  • Active Comparator: Cohort 1
    Cohort 1 (preconsented) patients will involve obtaining informed consent from the legally authorized representative of a potential study subject before they present to the ED in SE. Patient assent will be obtained for patients as per local IRB rules. The consent document (enclosed in this application) will inform parents that if their child comes to the ED and qualifies for the study based on study inclusion/exclusion criteria, they will be enrolled.
    Patients who cannot be contacted to confirm consent will be enrolled in Cohort 2 (EFIC) as detailed below.
    Patients in Cohort 1 will be randomized in a blinded fashion to either lorazepam 0.1 mg/kg or diazepam 0.2 mg/kg
  • Active Comparator: Cohort 2
    Cohort 2 (EFIC) will include patients who appear in the ED with SE and qualify for the study but have not given prior consent. These patients will be enrolled under the EFIC regulations. The parent/guardian will be given the opportunity to object to participation or ask additional questions.
    The child will be enrolled (dosed) with study medication under an EFIC. Once the child is stabilized, a research staff member will approach the parent or LAR to obtain informed consent to continue the child's participation in the study. If a parent or LAR refuses continued participation, then no further study procedures will be performed. Safety and data will be collected in accordance with federal regulations.
    Cohort 2 will be randomized, like Cohort 1, to either lorazepam 0.1 mg/kg or diazepam 0.2 mg/kg

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment259
Estimated Completion DateMay 2012
Estimated Primary Completion DateMay 2012
Eligibility Criteria
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;
GenderBoth
Ages3 Months
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Canada

Administrative Information[ + expand ][ + ]

NCT Number NCT00621478
Other Study ID NumbersN01HD043393
Has Data Monitoring CommitteeYes
Information Provided ByEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study SponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
CollaboratorsNot Provided
Investigators Principal Investigator: James Chamberlain, MD Children's Research Institute
Verification DateJuly 2012

Locations[ + expand ][ + ]

University of California- Davis Medical Center
Davis, California, United States, 95817
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Children's National Medical Center
Washington DC, District of Columbia, United States, 20010
University of Maryland Hospital for Children
Baltimore, Maryland, United States, 21201
University of Michigan Emergency Medicine Research
Ann Arbor, Michigan, United States, 48106
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
Children's Hospital of Buffalo
Buffalo, New York, United States, 14222
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Medical Center Dallas
Dallas, Texas, United States, 75390-9063
Texas Children's Hospital
Houston, Texas, United States, 77030
University of Utah Pediatric Emergency Medicine
Salt Lake City, Utah, United States, 84158
Medical College of Wisconsin Children's Corporate Center
Milwaukee, Wisconsin, United States, 53226
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B6A8
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H8L1