Status EpilepticusPhase 2/3NCT00621478
Efficacy and Safety Study Comparing Lorazepam and Diazepam for Children in the Emergency Department With Seizures (Status 2)
A Phase 2/3 study testing lorazepam or diazepam in people with Status Epilepticus, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 14 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- Status Epilepticus
- What is being tested?
- lorazepam or diazepam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Feb 2008to May 2012
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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:
- 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;
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States12 sites
University of Michigan Emergency Medicine Research
Ann Arbor, Michigan, 48106
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Maryland Hospital for Children
Baltimore, Maryland, 21201
Children's Hospital of Buffalo
Buffalo, New York, 14222
Children's Medical Center Dallas
Dallas, Texas, 75390-9063
University of California- Davis Medical Center
Davis, California, 95817
Children's Hospital of Michigan
Detroit, Michigan, 48201
Texas Children's Hospital
Houston, Texas, 77030
Medical College of Wisconsin Children's Corporate Center
Milwaukee, Wisconsin, 53226
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Utah Pediatric Emergency Medicine
Salt Lake City, Utah, 84158
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Canada2 sites
Alberta Children's Hospital
Calgary, Alberta, T3B6A8
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H8L1
About this study
Official title: Use Of Lorazepam For The Treatment Of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial Of Lorazepam And Diazepam
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.
Read the 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.
- Conditions
- Status Epilepticus
- Being tested
- lorazepam or diazepam
- Medical subject headings
- Status Epilepticus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lorazepam or diazepamDrug
Also called Ativan, Valium
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: lorazepam or diazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 minutes
Secondary outcomes (6)
To determine population pharmacokinetics (PK) of lorazepam using sparse sampling.
Measured: 24 hr
feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial
Measured: 2 years
the experience of community consultation and public disclosure
Measured: 2 years
feasibility of enrolling pediatric patients under an exception from informed consent
Measured: 2 years
determine patients' and parents' attitudes and reactions to an exception from informed consent approach
Measured: 2 years
severe or life-threatening respiratory depression
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Status EpilepticusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James Chamberlain, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621478
- Sponsor's protocol ID
- N01HD043393
- Other IDs
- 275200403393C
- Status last verified
- Jul 2012
- First submitted
- 20 Feb 2008
- Last updated
- 18 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27993298Chamberlain 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.
PubMed 24756515
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use Of Lorazepam For The Treatment Of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial Of Lorazepam And Diazepam
- ClinicalTrials.gov ID
- NCT00621478
- Acronym / sponsor ID
- N01HD043393
- Conditions
- Status Epilepticus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Feb 2008
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 22 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Active comparator | Drug: lorazepam or diazepamCohort 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 |
| Cohort 2 | Active comparator | Drug: lorazepam or diazepamCohort 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 |
Who may qualify
- Ages
- 3 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age 3 months to less than 18 years;
- Generalized tonic clonic status epilepticus, defined as:
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lorazepam or diazepamAlso: Ativan, ValiumAdministration 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. | Drug | Cohort 1, Cohort 2 |
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.
Time frame: 30 minutes
6 secondary outcomes
To determine population pharmacokinetics (PK) of lorazepam using sparse sampling.
Time frame: 24 hr
feasibility of identifying patients for informed consent prior to arrival in status epilepticus for a randomized controlled trial
Time frame: 2 years
the experience of community consultation and public disclosure
Time frame: 2 years
feasibility of enrolling pediatric patients under an exception from informed consent
Time frame: 2 years
determine patients' and parents' attitudes and reactions to an exception from informed consent approach
Time frame: 2 years
severe or life-threatening respiratory depression
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2012.
- Derived from this study: PubMed 27993298Chamberlain 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.
- Derived from this study: PubMed 24756515Chamberlain 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Chamberlain, MD principal investigator
Children's National Research Institute
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing lorazepam or diazepam in people with Status Epilepticus, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00621478, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2012.