Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures

NCT ID: NCT05670509

Last Updated: 2024-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 305 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-19
• Study Completion Date: 2022-07-31

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).

Conditions

Convulsions

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nasal administration of midazolam in home group

treatment with intranasal midazolam in children with known seizure disorder who were prescribed midazolam by pediatric neurologist at home with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) 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. children with known seizure disorder who were prescribed midazolam by pediatric neurologist

Group Type: EXPERIMENTAL

administration of Nasal midazolam in home group as a rescue medication for seizure control.

Intervention Type: DRUG

Children from home group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing

buccal administration of midazolam in home group

treatment with buccal midazolam in children with known seizure disorder who were prescribed midazolam by pediatric neurologist at home with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

Group Type: EXPERIMENTAL

administration of Buccal midazolam in home group as a rescue medication for seizure control.

Intervention Type: DRUG

Children from home group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

intramuscular administration of midazolam in home group

treatment with intramuscular midazolam in children with known seizure disorder who were prescribed midazolam by pediatric neurologist at home with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) administered via using 3 mm syringe in the front aspect of thigh

Group Type: EXPERIMENTAL

administration of intramuscular midazolam in homegroup as a rescue medication for seizure control.

Intervention Type: DRUG

Children from home group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh

Nasal administration of midazolam in ER group

treatment with intranasal midazolam in children presenting to ER with acute seizures with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) 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.

Group Type: EXPERIMENTAL

administration of Nasal midazolam in ER group as a rescue medication for seizure control.

Intervention Type: DRUG

Children from the ER group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing

buccal administration of midazolam in ER group

treatment with buccal midazolam in children presenting to ER with acute seizures with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

Group Type: EXPERIMENTAL

administration of Buccal midazolam in ER group as a rescue medication for seizure control.

Intervention Type: DRUG

Children from ER group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

Intramuscular administration of midazolam in ER group

treatment with intramuscular midazolam in children presenting to ER with acute seizures with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) administered via using 3 mm syringe in the front aspect of thigh

Group Type: EXPERIMENTAL

administration of intramuscular midazolam in ER group as a rescue medication for seizure control.

Intervention Type: DRUG

Children from ER group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh

Interventions

administration of Nasal midazolam in home group as a rescue medication for seizure control.

Children from home group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing

Intervention Type: DRUG

administration of Buccal midazolam in home group as a rescue medication for seizure control.

Children from home group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

Intervention Type: DRUG

administration of intramuscular midazolam in homegroup as a rescue medication for seizure control.

Children from home group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh

Intervention Type: DRUG

administration of Nasal midazolam in ER group as a rescue medication for seizure control.

Children from the ER group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing

Intervention Type: DRUG

administration of Buccal midazolam in ER group as a rescue medication for seizure control.

Children from ER group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe

Intervention Type: DRUG

administration of intramuscular midazolam in ER group as a rescue medication for seizure control.

Children from ER group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh

Intervention Type: DRUG

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Omnia El Rashidy, MD

Role: STUDY_CHAIR

Ain Shams University

Iman Ali, MD

Role: STUDY_CHAIR

Ain Shams University

Maha El Gafary, MD

Role: STUDY_CHAIR

Ain Shams University

Maha zakariya Mohammed, MD

Role: STUDY_CHAIR

Ain Shams University

Rana El Garhy, master

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health

Locations

Ain Shams Pediatric hospital

Cairo, , Egypt

Countries

Egypt

Other Identifiers

fmasu md 19 1 2019

Identifier Type: -

Identifier Source: org_study_id