Intranasal Midazolam Versus Rectal Diazepam for Treatment of Seizures

NCT ID: NCT00326612

Last Updated: 2011-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2008-12-31

Brief Summary

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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

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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.

Conditions

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Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intranasal Midazolam 0.2mg/kg

GIve once for seizure longer than 5 minutes

Group Type ACTIVE_COMPARATOR

Midazolam

Intervention Type DRUG

Intranasal Midazolam 0.2 mg/kg given once for seizures longer than 5 minutes.

Rectal Diazepam 0.3-0.5 mg/kg

Given once for seizure longer than 5 minutes

Group Type ACTIVE_COMPARATOR

Diazepam

Intervention Type DRUG

Rectal Diazepam (Diastat) given once for seizure greater than 5 minutes.

Interventions

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Midazolam

Intranasal Midazolam 0.2 mg/kg given once for seizures longer than 5 minutes.

Intervention Type DRUG

Diazepam

Rectal Diazepam (Diastat) given once for seizure greater than 5 minutes.

Intervention Type DRUG

Other Intervention Names

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Diastat Versed

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

1 Week

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Primary Children's Hospital

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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Maija Holsti

Associate Professor Division of Pediatric Emergency Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maija Holsti, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Francis Filloux, MD

Role: STUDY_CHAIR

University of Utah

Jeff Schunk, MD

Role: STUDY_CHAIR

University of Utah

Locations

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Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 15367152 (View on PubMed)

Starreveld E, Starreveld AA. Status epilepticus. Current concepts and management. Can Fam Physician. 2000 Sep;46:1817-23.

Reference Type BACKGROUND
PMID: 11013800 (View on PubMed)

Scheepers 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.

Reference Type BACKGROUND
PMID: 10985999 (View on PubMed)

Jeannet 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.

Reference Type BACKGROUND
PMID: 10700542 (View on PubMed)

Treatment 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.

Reference Type BACKGROUND
PMID: 8340986 (View on PubMed)

Chamberlain 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.

Reference Type BACKGROUND
PMID: 9127414 (View on PubMed)

Fisgin 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.

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Fisgin 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.

Reference Type BACKGROUND
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Kutlu 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.

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Lahat 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.

Reference Type BACKGROUND
PMID: 10884257 (View on PubMed)

Lahat 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.

Reference Type BACKGROUND
PMID: 10669200 (View on PubMed)

Lahat 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.

Reference Type BACKGROUND
PMID: 9746026 (View on PubMed)

Lahat 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.

Reference Type BACKGROUND
PMID: 9435015 (View on PubMed)

McGlone 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.

Reference Type BACKGROUND
PMID: 11354231 (View on PubMed)

Rainbow 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.

Reference Type BACKGROUND
PMID: 12410871 (View on PubMed)

Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet. 1999 Feb 20;353(9153):623-6. doi: 10.1016/S0140-6736(98)06425-3.

Reference Type BACKGROUND
PMID: 10030327 (View on PubMed)

Wallace SJ. Nasal benzodiazepines for management of acute childhood seizures? Lancet. 1997 Jan 25;349(9047):222. doi: 10.1016/S0140-6736(05)64856-8. No abstract available.

Reference Type BACKGROUND
PMID: 9014904 (View on PubMed)

Wroblewski BA, Joseph AB. The use of intramuscular midazolam for acute seizure cessation or behavioral emergencies in patients with traumatic brain injury. Clin Neuropharmacol. 1992 Feb;15(1):44-9. doi: 10.1097/00002826-199202000-00006.

Reference Type BACKGROUND
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Pellock JM. Status epilepticus in children: update and review. J Child Neurol. 1994 Oct;9 Suppl 2:27-35.

Reference Type BACKGROUND
PMID: 7806783 (View on PubMed)

Verity CM. Do seizures damage the brain? The epidemiological evidence. Arch Dis Child. 1998 Jan;78(1):78-84. doi: 10.1136/adc.78.1.78. No abstract available.

Reference Type BACKGROUND
PMID: 9534684 (View on PubMed)

Alldredge BK, Wall DB, Ferriero DM. Effect of prehospital treatment on the outcome of status epilepticus in children. Pediatr Neurol. 1995 Apr;12(3):213-6. doi: 10.1016/0887-8994(95)00044-g.

Reference Type BACKGROUND
PMID: 7619187 (View on PubMed)

Knoester PD, Jonker DM, Van Der Hoeven RT, Vermeij TA, Edelbroek PM, Brekelmans GJ, de Haan GJ. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. Br J Clin Pharmacol. 2002 May;53(5):501-7. doi: 10.1046/j.1365-2125.2002.01588.x.

Reference Type BACKGROUND
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Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav. 2004 Apr;5(2):253-5. doi: 10.1016/j.yebeh.2004.01.003.

Reference Type BACKGROUND
PMID: 15123028 (View on PubMed)

Vilke GM, Sharieff GQ, Marino A, Gerhart AE, Chan TC. Midazolam for the treatment of out-of-hospital pediatric seizures. Prehosp Emerg Care. 2002 Apr-Jun;6(2):215-7. doi: 10.1080/10903120290938571.

Reference Type BACKGROUND
PMID: 11962570 (View on PubMed)

Holsti M, Dudley N, Schunk J, Adelgais K, Greenberg R, Olsen C, Healy A, Firth S, Filloux F. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med. 2010 Aug;164(8):747-53. doi: 10.1001/archpediatrics.2010.130.

Reference Type DERIVED
PMID: 20679166 (View on PubMed)

Other Identifiers

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15275

Identifier Type: -

Identifier Source: org_study_id