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Effect of midazolam through nasal versus intravenous route in controlling seizures in children.

Phase 2/3
Not yet recruiting
Conditions
Disorder of central nervous system, unspecified,
Registration Number
CTRI/2024/01/061644
Lead Sponsor
Government medical college and hospital, Chandigarh
Brief Summary

A seizure is a neurological emergency in children that results from an uncontrolled or

synchronous electrical disturbance in the brain. These disturbances can cause a variety of

brief signs and symptoms, such as altered perception of sensations, confusion, uncontrollable

jerking movements, and loss of consciousness.

Delayed treatment has been associated with a higher risk of death, longer seizure duration,

and continuous administration of medication to stop seizures, all of which can result in

morphological cortical brain damage and might cause irreversible neuronal injury due to

excitotoxicity. Recent guidelines for managing seizures have placed a strong emphasis on

necessity to commence drug treatment as early as feasible to avoid complications. Prompt

and efficient treatment is necessary for children undergoing acute seizures to terminate

seizure activity and avert the development of prolonged seizures and status epilepticus. IV

administration of the drugs could be the best route to achieve this and is most used in routine

emergency practices. But in children with active seizures, gaining IV access can be

challenging especially in primary health centers and this might lead to significant delay in

seizure cessation. Additionally, the majority of seizure emergencies arise outside of medical

facilities, underscoring the importance of medical interventions that caregivers can swiftly

and securely administer. So other routes that are minimally invasive with similar efficacy like

buccal, intranasal, or rectal routes need to be considered.

Benzodiazepines are the first-line drugs for acute seizure control in children. Midazolam, a

short-acting benzodiazepine, being water and lipid soluble (physiological pH),

crosses nasal mucosa and blood-brain barrier causing a rapid rise in plasma and CSF

concentrations.  The administration of Buccal Midazolam is frequently impeded by

symptoms such as jaw clenching, excessive salivation, or involuntary swallowing. Following

nasal administration, midazolam has higher bioavailability, bypassing hepatic clearance.

Intranasal midazolam offers an excellent alternative especially for an out-of-hospital setting

and is socially acceptable unlike rectal midazolam. Approximately six minutes after

intranasal administration of 0.2 mg/kg, the plasma concentration of midazolam

reaches 100 ng/ml. However, IV midazolam is used in daily practices in our emergency

setting for children presenting with seizures which require the prompt establishment of

intravenous lines whereas IN formulations of midazolam, being non-invasive provide an

alternative strategy in this direction, and numerous studies were done to assess its anti-seizure

efficacy which have observed favorable outcomes, especially taking into account the

time required to establish IV line and patient considerations including patient positioning and

the need for privacy when employing the rectal mode of administration; IN midazolam may

prevent delay in commencing treatment.

Hence a comparison of the two different routes of administration is not possible unless RCT

is done wherein both routes are used in supervised emergency conditions. Compared to the

IV route, the use of IN midazolam is easier for parents and is more accessible. This

medication can be administered not only in medical centers but also at home, provided that

the parents of children with acute seizures receive appropriate instructions. The utilization of

intranasal midazolam for controlling acute seizures may lead to better patient care and

increased safety for healthcare professionals. There are reports in the literature regarding the

comparison of IN midazolam with other benzodiazepines used intravenously or other

routes, however, no data is available regarding the comparison of IN vs IV midazolam.

Therefore,“the purpose of this clinical trial is to assess the effectiveness of intranasal

midazolam in comparison to intravenous administration for treating acute seizures in

paediatric patients.

Detailed Description

Not available

Recruitment & Eligibility

Status
Not Yet Recruiting
Sex
All
Target Recruitment
30
Inclusion Criteria

All children between the ages of 1 month and 18 years presenting with acute seizures for at least 5 minutes duration in pediatric emergency and in patient department of GMCH 32, Chandigarh.

Exclusion Criteria
  1. Non consenting parents 2) Children <5kg weight 3) Children with upper respiratory tract infections 4) Children who had received anticonvulsants within 1 hour before admission 5) Children with severe cardiorespiratory decompensation 6) Children with CSF rhinorrhea 7) Known allergy to benzodiazepines.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Seizure cessationInterval between arrival of patients at the hospital with active seizures/ witnessed seizures more than 5 minutes and the control of seizures
Secondary Outcome Measures
NameTimeMethod
Incidence of adverse drug reactions among the patients receiving intranasal & intravenous midazolam.30 minutes

Trial Locations

Locations (1)

Government medical college and hospital, Chandigarh.

🇮🇳

Chandigarh, CHANDIGARH, India

Government medical college and hospital, Chandigarh.
🇮🇳Chandigarh, CHANDIGARH, India
DrSherlin JeberzhiahP
Principal investigator
9677683551
sherlinjeberzhiahp@gmail.com

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