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

NCT00621478 | Completed Phase 2 DMC

• 2 other identifiers: N01HD043393275200403393C
• Study Type: interventional
• Target: 259
• Locations: 2 countries
• Sites: 14

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.

Conditions

Status Epilepticus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

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

  24 hr

• 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

• feasibility of enrolling pediatric patients under an exception from informed consent

  2 years

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

  2 years

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

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

Cohort 2

ACTIVE COMPARATOR

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

Interventions

lorazepam or diazepam DRUG

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.

Also known as: Ativan, Valium

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 3 months to less than 18 years;
• Generalized tonic clonic status epilepticus, defined as:
• 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
• 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
• 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

You may not qualify if:

• 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 a benzodiazepine within 1 week of presentation.
• Pregnancy;
• Use of a benzodiazepine within 1 week of presentation.
• Parent/guardian refusal to give informed consent by the methods described;
• 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;

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (14)

University of California- Davis Medical Center

Davis, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Maryland Hospital for Children

Baltimore, Maryland, 21201, United States

Location

University of Michigan Emergency Medicine Research

Ann Arbor, Michigan, 48106, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75390-9063, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah Pediatric Emergency Medicine

Salt Lake City, Utah, 84158, United States

Location

Medical College of Wisconsin Children's Corporate Center

Milwaukee, Wisconsin, 53226, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B6A8, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H8L1, Canada

Location

Related Publications (2)

• Chamberlain DB, Chamberlain JM. Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus. Ann Emerg Med. 2017 Jan;69(1):117-124. doi: 10.1016/j.annemergmed.2016.08.449.

  PMID: 27993298 DERIVED

• Chamberlain JM, Okada P, Holsti M, Mahajan P, Brown KM, Vance C, Gonzalez V, Lichenstein R, Stanley R, Brousseau DC, Grubenhoff J, Zemek R, Johnson DW, Clemons TE, Baren J; Pediatric Emergency Care Applied Research Network (PECARN). Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA. 2014 Apr 23-30;311(16):1652-60. doi: 10.1001/jama.2014.2625.

  PMID: 24756515 DERIVED

MeSH Terms

Conditions

Status Epilepticus

Interventions

Lorazepam; Diazepam

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• James Chamberlain, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 22, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: December 18, 2012

Record last verified: 2012-07

Locations

CA (2); US (12)