SeizuresPhase 2NCT00326612
Intranasal Midazolam Versus Rectal Diazepam for Treatment of Seizures
A Phase 2 study testing Midazolam and Diazepam in people with Seizures, run by University of Utah at 1 site in United States.
Trial summary
The investigators will conduct a randomized controlled trial comparing the use of nasal midazolam, using a Mucosal Atomization Devise, to rectal diazepam for the treatment of acute seizure activity in children under the age of 18 years with epilepsy in the community setting. Read more about this study
- Who is it for?
- Ages 1 week to 17 years
- Conditions the study is for
- Seizures
- What is being tested?
- Midazolam and Diazepam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 358 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Dec 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 week to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children seventeen years and under will be identified through a Pediatric Neurology clinic at Primary Children's Medical Center,
- Known seizure disorder, AND
- Either have or will be prescribed a rescue anti-epileptic (rectal diazepam, or Diastat) for home use by their neurologist.
Who cannot join
- The neurologist does not prescribe a rescue medication for home use,
- 18 years of age or older,
- They have absence seizures, OR
- They have been prescribed lorazepam for home use for seizure activity.
Trial locations and contacts
1 site in 1 country.
United States1 site
Primary Children's Medical Center
Salt Lake City, Utah, 84113
About this study
Official title: Intranasal Midazolam Versus Rectal Diazepam for the Home Treatment of Seizure Activity in Pediatric Patients With Epilepsy
The investigators will conduct a randomized controlled trial comparing the use of nasal midazolam, using a Mucosal Atomization Devise, to rectal diazepam for the treatment of acute seizure activity in children under the age of 18 years with epilepsy in the community setting. The primary hypothesis is that nasal midazolam will be more effective and have shorter seizure time compared to rectal diazepam in the community. The secondary hypotheses are that patients treated with nasal midazolam will have fewer respiratory complications, emergency department visits, and admissions.
Read the detailed description
Study Design: This is a prospective randomized controlled study.
Study Procedures: Parents/guardians will be provided with a stopwatch to help record seizure times on the "Parent Form". All parents of children who have a seizure lasting longer than five minutes will be randomized to treat their seizure with the study medication (either rectal diazepam or nasal midazolam). If a parent treats a child with a study medication for seizure activity they are required to call "911". Families will be instructed to only give one dose of the study medication. If the seizure persists, EMS may give a second medication and transport the patient to the ED as per their established protocol. All parents/guardians who participate in this study will be asked to fill out a "Pre-study Form" (to be filled out during enrollment into the study) and a "Parent Form" for every seizure that is treated with the study medication. They will be given a stamped returned envelope to return the questionnaire. Once the study medication is used once, they will be done with the study. Any further need of home rescue medications to treat acute seizure activity will be coordinated by their neurologist. If questions arise, a study coordinator will be available by phone. In addition, parents/guardians will be contacted by phone every two months and questioned at clinic visits to audit compliance of reporting of seizures/hospitalizations, adverse events and answer any questions that arise. The study packet also instructs all families to call the study coordinator immediately if any expected or unexpected complication occurs. The study coordinator will be called on all ED visits and hospitalizations. We will then collect and analyze adverse events to compare them between the two groups. Any ER visit or hospitalization will be considered an adverse event and will be analyzed for its relationship to the seizure or medication. All adverse events will be reported to the IRB. See Table 1 for doses for the two study medications.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called Diastat
Intranasal Midazolam 0.2 mg/kg given once for seizures longer than 5 minutes.
DiazepamDrug
Also called Versed
Rectal Diazepam (Diastat) given once for seizure greater than 5 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Intranasal Midazolam 0.2mg/kg | Active comparator | GIve once for seizure longer than 5 minutes Receives: Drug: Midazolam |
| Rectal Diazepam 0.3-0.5 mg/kg | Active comparator | Given once for seizure longer than 5 minutes Receives: Drug: Diazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of Seizure After Study Medication Administration
Length of seizure.
Measured: 24 hours
Secondary outcomes (6)
Respiratory Depression Requiring Intubation
Respiratory depression was defined as intubation at Emergency Department discharge.
Measured: 24 hours
Number of Patients Who Needed Additional Medication to Treat the Seizure in the Emergency Department Within 24 Hours
Measured: 24 hours
Number of Patients Needed to be Seen or Treated in the Emergency Department for Their Seizure and Use of Study Medication.
Measured: 24 hours
Number of Patients That Were Admitted to the Hospital After Their Seizure and Use of Study Medication.
Measured: 24 hours
Number of Patients Who Had a Repeat Seizure Within 12 Hours After Their Seizure Who Used Study Medication
Measured: 12 hours
Respiratory Depression Requiring Oxygen at Discharge From the Emergency Department.
Respiratory depression was defined as requiring oxygen at discharge from the Emergency Department.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2006 (estimated)
- Study startJun 2006
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for SeizuresStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Primary Children's Hospital
- Responsible party
- Principal investigator, Maija Holsti, University of Utah
- Investigators
- Maija Holsti, MD, MPH, Principal investigator, University of UtahFrancis Filloux, MD, Study chair, University of UtahJeff Schunk, MD, Study chair, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00326612
- Sponsor's protocol ID
- 15275
- Status last verified
- Sep 2011
- First submitted
- 15 May 2006
- Last updated
- 26 Oct 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Harbord MG, Kyrkou NE, Kyrkou MR, Kay D, Coulthard KP. Use of intranasal midazolam to treat acute seizures in paediatric community settings. J Paediatr Child Health. 2004 Sep-Oct;40(9-10):556-8. doi: 10.1111/j.1440-1754.2004.00463.x.
PubMed 15367152Starreveld E, Starreveld AA. Status epilepticus. Current concepts and management. Can Fam Physician. 2000 Sep;46:1817-23.
PubMed 11013800Scheepers M, Scheepers B, Clarke M, Comish S, Ibitoye M. Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? Seizure. 2000 Sep;9(6):417-22. doi: 10.1053/seiz.2000.0425.
PubMed 10985999Jeannet PY, Roulet E, Maeder-Ingvar M, Gehri M, Jutzi A, Deonna T. Home and hospital treatment of acute seizures in children with nasal midazolam. Eur J Paediatr Neurol. 1999;3(2):73-7. doi: 10.1053/ejpn.1999.0185.
PubMed 10700542Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. 1993 Aug 18;270(7):854-9.
PubMed 8340986Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997 Apr;13(2):92-4. doi: 10.1097/00006565-199704000-00002.
PubMed 9127414Fisgin T, Gurer Y, Senbil N, Tezic T, Zorlu P, Okuyaz C, Akgun D. Nasal midazolam effects on childhood acute seizures. J Child Neurol. 2000 Dec;15(12):833-5. doi: 10.1177/088307380001501219.
PubMed 11198507Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, Akgun D. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol. 2002 Feb;17(2):123-6. doi: 10.1177/088307380201700206.
PubMed 11952072Kutlu NO, Yakinci C, Dogrul M, Durmaz Y. Intranasal midazolam for prolonged convulsive seizures. Brain Dev. 2000 Sep;22(6):359-61. doi: 10.1016/s0387-7604(00)00155-8.
PubMed 11042416Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000 Jul 8;321(7253):83-6. doi: 10.1136/bmj.321.7253.83.
PubMed 10884257Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Intranasal midazolam as a treatment of autonomic crisis in patients with familial dysautonomia. Pediatr Neurol. 2000 Jan;22(1):19-22. doi: 10.1016/s0887-8994(99)00109-5.
PubMed 10669200Lahat E, Goldman M, Barr J, Eshel G, Berkovitch M. Intranasal midazolam for childhood seizures. Lancet. 1998 Aug 22;352(9128):620. doi: 10.1016/S0140-6736(05)79574-X. No abstract available.
PubMed 9746026Lahat E. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997 Dec;13(6):449. No abstract available.
PubMed 9435015McGlone R, Smith M. Intranasal midazolam. An alternative in childhood seizures. Emerg Med J. 2001 May;18(3):234. doi: 10.1136/emj.18.3.234. No abstract available.
PubMed 11354231Rainbow J, Browne GJ, Lam LT. Controlling seizures in the prehospital setting: diazepam or midazolam? J Paediatr Child Health. 2002 Dec;38(6):582-6. doi: 10.1046/j.1440-1754.2002.00046.x.
PubMed 12410871
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Midazolam Versus Rectal Diazepam for the Home Treatment of Seizure Activity in Pediatric Patients With Epilepsy
- ClinicalTrials.gov ID
- NCT00326612
- Acronym / sponsor ID
- 15275
- Conditions
- Seizures
- Keywords
- Seizures
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 358 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Primary Children's Hospital
- Study start
- Jun 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 17 May 2006 (estimated)
- Results
- Posted 26 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will conduct a randomized controlled trial comparing the use of nasal midazolam, using a Mucosal Atomization Devise, to rectal diazepam for the treatment of acute seizure activity in children under the age of 18 years with epilepsy in the community setting. The primary hypothesis is that nasal midazolam will be more effective and have shorter seizure time compared to rectal diazepam in the community. The secondary hypotheses are that patients treated with nasal midazolam will have fewer respiratory complications, emergency department visits, and admissions.
Detailed description
Study Design: This is a prospective randomized controlled study.
Study Procedures: Parents/guardians will be provided with a stopwatch to help record seizure times on the "Parent Form". All parents of children who have a seizure lasting longer than five minutes will be randomized to treat their seizure with the study medication (either rectal diazepam or nasal midazolam). If a parent treats a child with a study medication for seizure activity they are required to call "911". Families will be instructed to only give one dose of the study medication. If the seizure persists, EMS may give a second medication and transport the patient to the ED as per their established protocol. All parents/guardians who participate in this study will be asked to fill out a "Pre-study Form" (to be filled out during enrollment into the study) and a "Parent Form" for every seizure that is treated with the study medication. They will be given a stamped returned envelope to return the questionnaire. Once the study medication is used once, they will be done with the study. Any further need of home rescue medications to treat acute seizure activity will be coordinated by their neurologist. If questions arise, a study coordinator will be available by phone. In addition, parents/guardians will be contacted by phone every two months and questioned at clinic visits to audit compliance of reporting of seizures/hospitalizations, adverse events and answer any questions that arise. The study packet also instructs all families to call the study coordinator immediately if any expected or unexpected complication occurs. The study coordinator will be called on all ED visits and hospitalizations. We will then collect and analyze adverse events to compare them between the two groups. Any ER visit or hospitalization will be considered an adverse event and will be analyzed for its relationship to the seizure or medication. All adverse events will be reported to the IRB. See Table 1 for doses for the two study medications.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intranasal Midazolam 0.2mg/kg | Active comparator | Drug: MidazolamGIve once for seizure longer than 5 minutes |
| Rectal Diazepam 0.3-0.5 mg/kg | Active comparator | Drug: DiazepamGiven once for seizure longer than 5 minutes |
Who may qualify
- Ages
- 1 week to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children seventeen years and under will be identified through a Pediatric Neurology clinic at Primary Children's Medical Center,
- Known seizure disorder, AND
- Either have or will be prescribed a rescue anti-epileptic (rectal diazepam, or Diastat) for home use by their neurologist.
Key exclusion criteria (4 listed)
- The neurologist does not prescribe a rescue medication for home use,
- 18 years of age or older,
- They have absence seizures, OR
- They have been prescribed lorazepam for home use for seizure activity.
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 |
|---|---|---|
| MidazolamAlso: DiastatIntranasal Midazolam 0.2 mg/kg given once for seizures longer than 5 minutes. | Drug | Intranasal Midazolam 0.2mg/kg |
| DiazepamAlso: VersedRectal Diazepam (Diastat) given once for seizure greater than 5 minutes. | Drug | Rectal Diazepam 0.3-0.5 mg/kg |
Primary outcome
Length of Seizure After Study Medication Administration
Time frame: 24 hours
Length of seizure.
6 secondary outcomes
Respiratory Depression Requiring Intubation
Time frame: 24 hours
Number of Patients Who Needed Additional Medication to Treat the Seizure in the Emergency Department Within 24 Hours
Time frame: 24 hours
Number of Patients Needed to be Seen or Treated in the Emergency Department for Their Seizure and Use of Study Medication.
Time frame: 24 hours
Number of Patients That Were Admitted to the Hospital After Their Seizure and Use of Study Medication.
Time frame: 24 hours
Number of Patients Who Had a Repeat Seizure Within 12 Hours After Their Seizure Who Used Study Medication
Time frame: 12 hours
Respiratory Depression Requiring Oxygen at Discharge From the Emergency Department.
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15367152Harbord MG, Kyrkou NE, Kyrkou MR, Kay D, Coulthard KP. Use of intranasal midazolam to treat acute seizures in paediatric community settings. J Paediatr Child Health. 2004 Sep-Oct;40(9-10):556-8. doi: 10.1111/j.1440-1754.2004.00463.x.
- Background: PubMed 11013800Starreveld E, Starreveld AA. Status epilepticus. Current concepts and management. Can Fam Physician. 2000 Sep;46:1817-23.
- Background: PubMed 10985999Scheepers M, Scheepers B, Clarke M, Comish S, Ibitoye M. Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? Seizure. 2000 Sep;9(6):417-22. doi: 10.1053/seiz.2000.0425.
- Background: PubMed 10700542Jeannet PY, Roulet E, Maeder-Ingvar M, Gehri M, Jutzi A, Deonna T. Home and hospital treatment of acute seizures in children with nasal midazolam. Eur J Paediatr Neurol. 1999;3(2):73-7. doi: 10.1053/ejpn.1999.0185.
- Background: PubMed 8340986Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. 1993 Aug 18;270(7):854-9.
- Background: PubMed 9127414Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997 Apr;13(2):92-4. doi: 10.1097/00006565-199704000-00002.
- Background: PubMed 11198507Fisgin T, Gurer Y, Senbil N, Tezic T, Zorlu P, Okuyaz C, Akgun D. Nasal midazolam effects on childhood acute seizures. J Child Neurol. 2000 Dec;15(12):833-5. doi: 10.1177/088307380001501219.
- Background: PubMed 11952072Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, Akgun D. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol. 2002 Feb;17(2):123-6. doi: 10.1177/088307380201700206.
- Background: PubMed 11042416Kutlu NO, Yakinci C, Dogrul M, Durmaz Y. Intranasal midazolam for prolonged convulsive seizures. Brain Dev. 2000 Sep;22(6):359-61. doi: 10.1016/s0387-7604(00)00155-8.
- Background: PubMed 10884257Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000 Jul 8;321(7253):83-6. doi: 10.1136/bmj.321.7253.83.
- Background: PubMed 10669200Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Intranasal midazolam as a treatment of autonomic crisis in patients with familial dysautonomia. Pediatr Neurol. 2000 Jan;22(1):19-22. doi: 10.1016/s0887-8994(99)00109-5.
- Background: PubMed 9746026Lahat E, Goldman M, Barr J, Eshel G, Berkovitch M. Intranasal midazolam for childhood seizures. Lancet. 1998 Aug 22;352(9128):620. doi: 10.1016/S0140-6736(05)79574-X. No abstract available.
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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.
Maija Holsti, MD, MPH principal investigator
University of Utah
Francis Filloux, MD study chair
University of Utah
Jeff Schunk, MD study chair
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midazolam and Diazepam in people with Seizures, run by University of Utah at 1 site in United States.
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 3 inclusion and 4 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 26 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Length of Seizure After Study Medication Administration (time frame: 24 hours). 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 NCT00326612, which also lists 25 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 26 Oct 2011.