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Status EpilepticusPhase 2NCT04926844

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

A Phase 2 study testing Levetiracetam and Midazolam in people with Status Epilepticus and Generalized Convulsive Status Epilepticus, run by Sohag University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 1 month to 16 years
What is being tested?
Levetiracetam and Midazolam
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
144 participants
Where
1 siteEgypt
Study dates
20 Jun 2021to 1 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Egypt1 site

  • Department of Pediatrics - Sohag University Hospital

    Sohag, 82524

Other trials in Egypt

About this study

Official title: 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.

Read the 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.

Being tested
Levetiracetam, Midazolam, Placebo
Keywords
Status epilepticus, Convulsions, Children, Seizures, Benzodiazepines, Midazolam, Levetiracetam
Medical subject headings
Status Epilepticus, Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevetiracetamDrug

    Also called Keppra, Tiratam

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

  • MidazolamDrug

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

  • PlaceboDrug

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

Study groups in NCT04926844
Study groupRoleWhat they receive
Study groupExperimentalChildren receiving levetiracetam + midazolam
Receives: Drug: Levetiracetam; Drug: Midazolam
Control groupPlacebo comparatorChildren receiving placebo + midazolam
Receives: Drug: Midazolam; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cessation of seizures

    Cessation of clinical seizures at 20 minutes timepoint (end of first therapy phase)

    Measured: 20 minutes

Secondary outcomes (8)

  1. Need for repeating midazolam

    Need for repeating midazolam during the first therapy phase (5 - 20 min)

    Measured: 20 minutes

  2. Cessation of seizures

    Cessation of clinical seizures at 40 minutes timepoint (end of second therapy phase).

    Measured: 40 minutes

  3. Seizure control

    24-hours seizure control (no visually observed recurrence of seizures after the end of second phase therapy with improved sensorium)

    Measured: 24 hours

  4. Hypotension

    Occurrence of hypotension

    Measured: 24 hours

  5. Need for mechanical ventilation

    Need for mechanical ventilation

    Measured: 24 hours

  6. Skin rash

    Occurrence of skin rash

    Measured: 24 hours

  7. Agitation/aggression

    Occurrence of agitation/aggression

    Measured: 24 hours

  8. Mortality

    Occurrence of death

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2021
  2. Study start20 Jun 2021
  3. Primary completion30 Aug 2022
  4. Study completion1 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
144 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04926844
Sponsor's protocol ID
Soh-Med-21-06-07
Status last verified
Sep 2022
First submitted
14 Jun 2021
Last updated
21 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Unidentified individual patients' data will be available on resonable request after publication

Publications

  • 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.

    PubMed 26900382

  • 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.

    PubMed 33552322

  • 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.

    PubMed 31879852

  • 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.

    PubMed 30472551

  • 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.

    PubMed 26627366

  • 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.

    PubMed 26840871

  • 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.

    PubMed 15210974

  • 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.

    PubMed 12915336

  • 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.

    PubMed 21898137

  • 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.

    PubMed 32385134

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Levetiracetam and Midazolam in people with Status Epilepticus and Generalized Convulsive Status Epilepticus, run by Sohag University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cessation of seizures (time frame: 20 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04926844, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2022; AzTrials last refreshed its copy on 8 Nov 2026.

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