Effectiveness of Combined Levetiracetam and Midazolam in Generalized Convulsive Status Epilepticus in Children

September 17, 2022 updated by: Ahmed Abdelhamid Elshater, Sohag University

Effectiveness of Combined Levetiracetam and Midazolam in Treatment of Generalized Convulsive Status Epilepticus in Children

Generalized status epilepticus is a common pediatric neurological emergency with significant mortality and morbidity. Benzodiazepines remain the first anticonvulsive line but benzo-diazepines don't control seizures in about 30% of cases. GCSE may be more rapidly stopped and controlled through combining another drug with benzodiazepines such as Levetiracetam, acting by different pathways. This study aims to evaluate the effectiveness of combined levetiracetam and midazolam in treatment of generalized convulsive status epilepticus in children.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Generalized convulsive status epilepticus (GCSE) is a common pediatric neurological emergency with an annual incidence of up to 73 episodes per 100,000 children and is associated with mortality in 2.7% of cases and overall morbidity in 10% - 20% of cases, including hemodynamic instability and long-term neurological impairments.

The management of GCSE in children starts with emergency measures (stabilization phase) with monitoring and laboratory testing in the first 5 minutes. Benzodiazepines are used as first-line anticonvulsants for GCSE that persists for more than 5 minutes. However, studies have shown that benzo-diazepines don't control GCSE in about 30% of patients. GCSE may be more rapidly stopped and controlled through combining another drug with benzodiazepines, acting by different pathways.

Levetiracetam is a recent broad-spectrum antiepileptic drug with a relatively high safety profile. The effectiveness of intravenous levetiracetam has been demonstrated as a second-line anticonvulsant in GCSE. In this study, we aim to evaluate the effectiveness and safety of levetiracetam plus midazolam versus midazolam alone as first-line therapy of GCSE in children.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Sohag, Egypt, 82524
        • Department of Pediatrics - Sohag University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 16 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Generalized convulsive status epilepticus, which is clinically defined at the time of presentation as continuous, generalized, tonic-clonic seizure activity or ≥ 2 generalized tonic-clonic seizures without recovery of consciousness for more than 5 minutes.

Exclusion Criteria:

  • Failure to obtain informed consent.
  • Prior therapy with any anticonvulsant for the presenting episode of generalized convulsive status epilepticus.
  • Epileptic patients on levetiracetam therapy.
  • Known allergy or contraindications to any of the study drugs.
  • End-stage kidney disease.
  • Severe liver disease.
  • Cardiac diseases.
  • Hypoglycemia or hyperglycemia.
  • Inborn errors of metabolism.
  • Known mood/behavioral disorder.
  • Failure to obtain intravenous access in the first 5 minutes.
  • Cessation of seizures during the stabilization phase (0 - 5 minutes).
  • Traumatic brain injury

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study group
Children receiving levetiracetam + midazolam
Drug: Levetiracetam
Intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).
Other Names:
  • Keppra
  • Tiratam
Drug: Midazolam
Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes
Placebo Comparator: Control group
Children receiving placebo + midazolam
Drug: Midazolam
Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes
Drug: Placebo
Intravenous isotonic saline (1.2 ml/kg) over 5 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cessation of seizures
Time Frame: 20 minutes
Cessation of clinical seizures at 20 minutes timepoint (end of first therapy phase)
20 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Need for repeating midazolam
Time Frame: 20 minutes
Need for repeating midazolam during the first therapy phase (5 - 20 min)
20 minutes
Cessation of seizures
Time Frame: 40 minutes
Cessation of clinical seizures at 40 minutes timepoint (end of second therapy phase).
40 minutes
Seizure control
Time Frame: 24 hours
24-hours seizure control (no visually observed recurrence of seizures after the end of second phase therapy with improved sensorium)
24 hours
Hypotension
Time Frame: 24 hours
Occurrence of hypotension
24 hours
Need for mechanical ventilation
Time Frame: 24 hours
Need for mechanical ventilation
24 hours
Skin rash
Time Frame: 24 hours
Occurrence of skin rash
24 hours
Agitation/aggression
Time Frame: 24 hours
Occurrence of agitation/aggression
24 hours
Mortality
Time Frame: 24 hours
Occurrence of death
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sohag University

Investigators

  • Study Chair: Abdelrahim A Sadek, MD, PhD, Sohag University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2021

Primary Completion (Actual)

August 30, 2022

Study Completion (Actual)

September 1, 2022

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 14, 2021

First Posted (Actual)

June 15, 2021

Study Record Updates

Last Update Posted (Actual)

September 21, 2022

Last Update Submitted That Met QC Criteria

September 17, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Soh-Med-21-06-07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Unidentified individual patients' data will be available on resonable request after publication

IPD Sharing Time Frame

After publication for 3 years

IPD Sharing Access Criteria

Contact the principal investigator

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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