Clinical trial NCT05670509: Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures
Official title: Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Egyptian Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Convulsions
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-01-04
Enrollment: 305
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two major groups were included (home and ER group) and each were subdivided into 3 groups according to route of administration (nasal, buccal and IM)
Primary purpose: TREATMENT

Brief summary: A randomized controlled clinical trial comparing patient/ ER physician satisfaction and ease of administration of 3 non IV routes of midazolam as a rescue medication for seizure control. Study population included children with known seizure disorder who were prescribed midazolam by pediatric neurologist at home and those presenting to ER with following inclusion and exclusion criteria

Detailed description: Recruited patients randomized using previously computer-generated randomization tables prepared by expert statistician. Study was approved by the faculty ethical committee prior to its start and oral informed consent was obtained from the parents. In order to simplify the administration process a reference guide was prepared for doses according to weight for each of the 3 routes.

Two major groups were included (home and ER group) and each were subdivided into 3 groups according to route of administration

Children was randomly assigned to receive treatment with intranasal, intramuscular or buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) .Intranasal form was administered via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5mg/spray). If the volume to be administered exceeded 1 mL, then the dose was divided between both nostrils to avoid runoff and swallowing. Administration was via sprays in each nostril (for nasal) or dripping between the cheek and the gum per side using insulin syringe (for buccal) or using 3 mm syringe in the front aspect of thigh for intramuscular injection.

Caretakers who gave the study medication recorded their observations and answered a series of questions regarding time to drug administration, seizure cessation time, seizure recurrence, need for hospitalization or ER visits and any encountered difficulties or side effects. Ease of administration of was rated using a scale prepared by expert statistian from very easy to very difficult and overall satisfaction with the medication was rated using 10-point nominal scale (0, being not satisfied and 10, greatly satisfied). Seizures that did not cease for ten minutes after drug administration and the need to use additional medication was categorized as a treatment failure criteria.

Recruited caretakers who did not spontaneously report the use of the study medication were contacted by phone monthly to address any questions and to remind them of the study. Problems with different routes of delivery were discussed, for example excessive head movements, ryle or upper respiratory tract infections and where possible suggestions and advices to help with addressed issue was provided .If a caretaker reported use of study medication at the time of the phone call, information was obtained at that time. In this group, not all children received a benzodiazepine because of different reasons: unavailability of the drug at home or at school, spontaneous resolution of seizures, difficulty in administrating the drug, or panic.

ER doctor given a brief survey after the administration to evaluate sedation, discomfort and other adverse effects of the medication as well as any administration difficulties and data for other secondary outcomes (need for additional medical support, hospitalization, repeated seizures...etc).

Eligibility criteria: Inclusion Criteria:

* Children aged between 1 months and 17 years
* children with known seizure disorder who were prescribed midazolam by pediatric neurologist at home
* Patients with generalized tonic-clonic status epilepticus with seizures accompanied by loss of consciousness with any of the following characteristics persistent at the time of study drug administration:

  1. Currently presenting with seizure (convulsive) activity and 3 or more convulsions within the preceding hour
  2. Currently presenting with seizure (convulsive) and 2 or more convulsions in succession without recovery of consciousness
  3. Currently presenting with a single seizure (convulsive) lasting \>=5 minutes

Exclusion Criteria:

* Any child who had received an anticonvulsant benzodiazepine agent within 1 hour of presentation
* Patients with known history of hypersensitivities, non-responsiveness or contraindications to benzodiazepines (i.e., clinically significant respiratory depression, severe acute hepatic failure, myasthenia gravis, syndrome of sleep apnea, glaucoma with closed angle, use of concomitant drugs determined by the investigator to have a contraindication to the use of bbenzodiazepines.)
* Patients with significant hypotension and cardiac dysrhythmia (e.g. atrioventricular block of second or third degree, ventricular tachycardia\]).
* Patients with current hypoglycemia (glucose \<60 milligram per deciliter \[mg/dl\]) on presentation at the hospital or healthcare setting.

Primary outcomes:
measure: Percentage of participants with therapeutic success
timeFrame: 30 minutes post drug administration
Secondary outcomes:
measure: sustained absence of seizure activity for at least 1 hour
timeFrame: from start of study drug administration up to 1 hour postdose
measure: sustained absence of seizure activity for 4 hour
timeFrame: from start of study drug administration up to 4 hours postdose
measure: sustained absence of seizure activity for 6 hour
timeFrame: from start of study drug administration up to 6 hours postdose
measure: Time to resolution of seizures (convulsions)
timeFrame: 30 minutes
measure: Time of drug preparation and administration
timeFrame: 45 minutes
measure: Emergency department visits
timeFrame: 24 hours post drug administration
measure: percentage of patients admitted to hospital
timeFrame: 24 hours post drug administration
measure: need for additional doses or additional drugs for seizure control
timeFrame: 10 minutes post drug administration
measure: Seizure recurrence at 1 ,4 , 6 and 24 hrs
timeFrame: 24 hours post drug administration
measure: Respiratory depression
timeFrame: 6 hours post drug administration
measure: Sedation or agitation
timeFrame: 4 hours post drug administration
measure: Frequency of cardio-respiratory side effects
timeFrame: 6 hours post drug administration
measure: Occurrence of route of administration and benzodiazepine related side effects
timeFrame: 6 hours post drug administration
measure: Caretakers and physicians ease of administration and satisfaction with the medication
timeFrame: up to 1 months after drug administration
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams Pediatric hospital
Study officials:
affiliation: Ain Shams University
name: Omnia El Rashidy, MD
role: STUDY_CHAIR
affiliation: Ain Shams University
name: Iman Ali, MD
role: STUDY_CHAIR
affiliation: Ain Shams University
name: Maha El Gafary, MD
role: STUDY_CHAIR
affiliation: Ain Shams University
name: Maha zakariya Mohammed, MD
role: STUDY_CHAIR
affiliation: Ministry of Health
name: Rana El Garhy, master
role: PRINCIPAL_INVESTIGATOR
References: