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Levetiracetam and Midazolam vs Midazolam Alone for First-Line Treatment of Children With Generalized Convulsive Status Epilepticus (Lev-Mid Study): A Randomized Controlled Trial

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Abstract

Background

Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE.

Objectives

To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE.

Design

Double-blind randomized controlled trial.

Setting

Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022.

Participants

Children aged between 1 month and 16 years with GCSE lasting more than 5 min.

Interventions

Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (Pla-Mid group) as first-line anticonvulsive therapy.

Outcome measures

Primary: cessation of clinical seizures at 20-min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects.

Results

Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the Pla-Mid group [RR (95% CI) 1.1 (0.9–1.34); P=0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58–1.11); P=0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96–1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94–1.3); P=0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13–1.92); P=0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe.

Conclusion

Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.

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Acknowledgment

Prof. Henry Silverman (University of Maryland), Dr. Maha Zakaria, Dr. Sara Makkia, and Dr. Sawsan Elateek (Ain-Shams University), Dr. Fatma Abdelgawad (Cairo University), and all the attendees of the MERETI scientific writing workshop (20–23 Oct 2022, Cairo) for their useful comments and feedback, which helped us improve scientific writing of this paper. Ethics clearance: Medical Research Ethics Committee, Faculty of Medicine, Sohag University; No: Soh-Med-21-06-07; dated June 10, 2021

Funding

Funding: None

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, 82524, Egypt

    Ahmed A. Elshater, Abdelrahim A. Sadek &  Elsayed Abdelkreem

Authors
  1. Ahmed A. Elshater
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  2. Abdelrahim A. Sadek
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  3. Elsayed Abdelkreem
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Contributions

Contributors: AAE: study design, data collection, statistical analysis; AAS: study concept and design, supervision; EA, study concept and design, data collection, statistical analysis, data interpretation, manuscript writing. All authors approved the final version of manuscript and are accountable for all aspects related to the study.

Corresponding author

Correspondence to Elsayed Abdelkreem.

Ethics declarations

Competing interests: None stated.

Additional information

Note: Additional material related to this study is available with the online version at http://www.indianpediatrics.net

Trial registration: ClinicalTrials.gov: NCT04926844.

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Elshater, A.A., Sadek, A.A. & Abdelkreem, E. Levetiracetam and Midazolam vs Midazolam Alone for First-Line Treatment of Children With Generalized Convulsive Status Epilepticus (Lev-Mid Study): A Randomized Controlled Trial. Indian Pediatr 60, 630–636 (2023). https://doi.org/10.1007/s13312-023-2960-8

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  • DOI: https://doi.org/10.1007/s13312-023-2960-8

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