Intranasal Midazolam Versus Rectal Diazepam for Treatment of Seizures

Seizures Clinical Trial

Official title:

Intranasal Midazolam Versus Rectal Diazepam for the Home Treatment of Seizure Activity in Pediatric Patients With Epilepsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00326612
• Other study ID #: 15275
• Status: Completed
• Phase: Phase 2
• First received: May 15, 2006
• Last updated: September 19, 2011
• Start date: June 2006
• Est. completion date: December 2008

Study information

• Verified date: September 2011
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 358
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Seizures

Intervention

Drug:
• Midazolam
Intranasal Midazolam 0.2 mg/kg given once for seizures longer than 5 minutes.
• Diazepam
Rectal Diazepam (Diastat) given once for seizure greater than 5 minutes.

Locations

Country	Name	City	State
United States	Primary Children's Medical Center	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Primary Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (24)

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. — View Citation

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. — View Citation

Fisgin T, Gürer Y, Senbil N, Teziç T, Zorlu P, Okuyaz C, Akgün D. Nasal midazolam effects on childhood acute seizures. J Child Neurol. 2000 Dec;15(12):833-5. — View Citation

Fisgin T, Gurer Y, Teziç T, Senbil N, Zorlu P, Okuyaz C, Akgün 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kutlu NO, Yakinci C, Dogrul M, Durmaz Y. Intranasal midazolam for prolonged convulsive seizures. Brain Dev. 2000 Sep;22(6):359-61. — View Citation

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. — View Citation

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. — View Citation

Lahat E, Goldman M, Barr J, Eshel G, Berkovitch M. Intranasal midazolam for childhood seizures. Lancet. 1998 Aug 22;352(9128):620. — View Citation

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. — View Citation

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. — View Citation

McGlone R, Smith M. Intranasal midazolam. An alternative in childhood seizures. Emerg Med J. 2001 May;18(3):234. — View Citation

Pellock JM. Status epilepticus in children: update and review. J Child Neurol. 1994 Oct;9 Suppl 2:27-35. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. Review. — View Citation

Verity CM. Do seizures damage the brain? The epidemiological evidence. Arch Dis Child. 1998 Jan;78(1):78-84. Review. — View Citation

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. — View Citation

Wallace SJ. Nasal benzodiazepines for management of acute childhood seizures? Lancet. 1997 Jan 25;349(9047):222. — View Citation

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. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Seizure After Study Medication Administration	Length of seizure.	24 hours	Yes
Secondary	Respiratory Depression Requiring Intubation	Respiratory depression was defined as intubation at Emergency Department discharge.	24 hours	Yes
Secondary	Number of Patients Who Needed Additional Medication to Treat the Seizure in the Emergency Department Within 24 Hours		24 hours	Yes
Secondary	Number of Patients Needed to be Seen or Treated in the Emergency Department for Their Seizure and Use of Study Medication.		24 hours	Yes
Secondary	Number of Patients That Were Admitted to the Hospital After Their Seizure and Use of Study Medication.		24 hours	Yes
Secondary	Number of Patients Who Had a Repeat Seizure Within 12 Hours After Their Seizure Who Used Study Medication		12 hours	No
Secondary	Respiratory Depression Requiring Oxygen at Discharge From the Emergency Department.	Respiratory depression was defined as requiring oxygen at discharge from the Emergency Department.	24 hours	Yes