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

NCT ID: NCT04926844

Last Updated: 2022-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-20

Study Completion Date

2022-09-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Status Epilepticus Generalized Convulsive Status Epilepticus Status Epilepticus, Generalized Status Epilepticus, Generalized Convulsive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two groups of children with continuing seizures after stabilization phase (5 minutes):

1. Study group; will receive intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).
2. Control group will receive intravenous isotonic saline (as a placebo) in the same way. At the same time, both groups will receive intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Each enrolled child will be assigned a unique identification number. Pharmacy will fill the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, and investigators will be unaware of group assignment and drug/placebo therapy.

Study Groups

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Study group

Children receiving levetiracetam + midazolam

Group Type EXPERIMENTAL

Levetiracetam

Intervention Type DRUG

Intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).

Midazolam

Intervention Type DRUG

Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes

Control group

Children receiving placebo + midazolam

Group Type PLACEBO_COMPARATOR

Midazolam

Intervention Type DRUG

Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes

Placebo

Intervention Type DRUG

Intravenous isotonic saline (1.2 ml/kg) over 5 minutes

Interventions

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Levetiracetam

Intravenous levetiracetam 60 mg/kg (max 4500 mg) over 5 minutes (diluted with isotonic saline to a concentration of 50 mg/ml).

Intervention Type DRUG

Midazolam

Intravenous midazolam 0.2 mg/kg (maximum 10 mg) over 2 minutes

Intervention Type DRUG

Placebo

Intravenous isotonic saline (1.2 ml/kg) over 5 minutes

Intervention Type DRUG

Other Intervention Names

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Keppra Tiratam

Eligibility Criteria

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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
Minimum Eligible Age

1 Month

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Ahmed Abdelhamid Elshater

Pediatric Resident

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Abdelrahim A Sadek, MD, PhD

Role: STUDY_CHAIR

Sohag University

Locations

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Department of Pediatrics - Sohag University Hospital

Sohag, , Egypt

Site Status

Countries

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Egypt

References

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Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61. doi: 10.5698/1535-7597-16.1.48.

Reference Type BACKGROUND
PMID: 26900382 (View on PubMed)

McKenzie KC, Hahn CD, Friedman JN. Emergency management of the paediatric patient with convulsive status epilepticus. Paediatr Child Health. 2021 Jan 21;26(1):50-66. doi: 10.1093/pch/pxaa127. eCollection 2021 Feb.

Reference Type BACKGROUND
PMID: 33552322 (View on PubMed)

Singh A, Stredny CM, Loddenkemper T. Pharmacotherapy for Pediatric Convulsive Status Epilepticus. CNS Drugs. 2020 Jan;34(1):47-63. doi: 10.1007/s40263-019-00690-8.

Reference Type BACKGROUND
PMID: 31879852 (View on PubMed)

Hamano SI, Sugai K, Miki M, Tabata T, Fukuyama T, Osawa M. Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus. J Neurol Sci. 2019 Jan 15;396:150-158. doi: 10.1016/j.jns.2018.09.035. Epub 2018 Oct 4.

Reference Type BACKGROUND
PMID: 30472551 (View on PubMed)

Navarro V, Dagron C, Elie C, Lamhaut L, Demeret S, Urien S, An K, Bolgert F, Treluyer JM, Baulac M, Carli P; SAMUKeppra investigators. Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2016 Jan;15(1):47-55. doi: 10.1016/S1474-4422(15)00296-3. Epub 2015 Nov 28.

Reference Type BACKGROUND
PMID: 26627366 (View on PubMed)

Alvarez V, Rossetti AO. Monotherapy or Polytherapy for First-Line Treatment of SE? J Clin Neurophysiol. 2016 Feb;33(1):14-7. doi: 10.1097/WNP.0000000000000217.

Reference Type BACKGROUND
PMID: 26840871 (View on PubMed)

Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6. doi: 10.1073/pnas.0308208101. Epub 2004 Jun 21.

Reference Type BACKGROUND
PMID: 15210974 (View on PubMed)

Klitgaard H, Pitkanen A. Antiepileptogenesis, neuroprotection, and disease modification in the treatment of epilepsy: focus on levetiracetam. Epileptic Disord. 2003 May;5 Suppl 1:S9-16.

Reference Type BACKGROUND
PMID: 12915336 (View on PubMed)

Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study. J Neurol. 2012 Apr;259(4):645-8. doi: 10.1007/s00415-011-6227-2. Epub 2011 Sep 6.

Reference Type BACKGROUND
PMID: 21898137 (View on PubMed)

Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, Kuperman R, Harbert MJ, Michelson D, Joe P, Wang S, Rismanchi N, Le NM, Mower A, Kim J, Battin MR, Lane B, Honold J, Knodel E, Arnell K, Bridge R, Lee L, Ernstrom K, Raman R, Haas RH; NEOLEV2 INVESTIGATORS. Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 Jun;145(6):e20193182. doi: 10.1542/peds.2019-3182. Epub 2020 May 8.

Reference Type BACKGROUND
PMID: 32385134 (View on PubMed)

Other Identifiers

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Soh-Med-21-06-07

Identifier Type: -

Identifier Source: org_study_id

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