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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00621478
First received: February 20, 2008
Last updated: December 14, 2012
Last verified: July 2012
  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.


Condition Intervention Phase
Status Epilepticus
Drug: lorazepam or diazepam
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Use Of Lorazepam For The Treatment Of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial Of Lorazepam And Diazepam

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • 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. [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]

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 ]

Enrollment: 259
Study Start Date: February 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

Other Names:
  • Ativan
  • Valium
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

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.

Other Names:
  • Ativan
  • Valium

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.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621478

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

No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00621478     History of Changes
Other Study ID Numbers: N01HD043393, 275200403393C
Study First Received: February 20, 2008
Last Updated: December 14, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Status Epilepticus
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Diazepam
Lorazepam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Muscle Relaxants, Central
Neuromuscular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 28, 2014