Generalized Convulsive Status EpilepticusPhase 2/3KLaSSECNCT07046611
Ketamine and Levetiracetam as Second-line Antiseizure Medication for Status Epilepticus in Children
A Phase 2/3 study testing Ketamine and Levetiracetam in people with Generalized Convulsive Status Epilepticus, run by Sohag University at 1 site in Egypt.
Trial summary
About 40% of children with generalized convulsive status epilepticus (GCSE) are not terminated by first-line benzodiazepines (BDZs), and approximately 50% of BDZ-refractory GCSE are not controlled by second-line antiseizure medications. This study investigates the efficacy of ketamine-levetiracetam combination vs. Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Generalized Convulsive Status Epilepticus
- What is being tested?
- Ketamine and Levetiracetam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteEgypt
- Study dates
- 2 Jul 2025to 1 Jul 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 year to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age from 1 year to 16 years.
- Generalized convulsive status epilepticus (GCSE), defined as clinically observed generalized tonic-clonic convulsions that continue or recur without complete regaining of consciousness in between for longer than 5 minutes.
- Benzodiazepine-refractory, defined as continuous or recurrent GCSE in the emergency room after receiving an adequate benzodiazepine dose, with the last dose administered within 5 to 30 minutes.
Who cannot join
- Failure to obtain informed consent.
- Prior treatment with antiseizure medication or anticonvulsant sedatives other than benzodiazepines for the presenting GCSE episode.
- Endotracheal intubation before enrollment.
- Acute traumatic brain injury.
- Cardiac arrest/post-anoxic seizures
- Hypoglycemia or hyperglycemia.
- Known allergies or contraindications to ketamine or levetiracetam
- Failure to obtain intravenous access.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site, 1 recruiting
- Recruiting
Department of Pediatrics at Sohag University Hospital
Sohag, 82524
Abdelrahim A Sadek, MD, PhD, abdoneurology@yahoo.com
About this study
Official title: Efficacy of Combined Ketamine and Levetiracetam as a Second-line Anti-seizure Medication for Generalized Convulsive Status Epilepticus in Children
About 40% of children with generalized convulsive status epilepticus (GCSE) are not terminated by first-line benzodiazepines (BDZs), and approximately 50% of BDZ-refractory GCSE are not controlled by second-line antiseizure medications. This study investigates the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE.
Read the detailed description
Generalized convulsive status epilepticus (GCSE) is the most common pediatric neurological emergency. Benzodiazepines (BDZs) are the recommended first-line anti-seizure medication (ASM) for GCSE, but they fail to halt seizures in about 40% of cases. Moreover, approximately 50% of BDZ-refractory GCSE are not terminated by second-line ASMs, including levetiracetam, valproate, and phenytoin. Continuous GCSE for a longer duration is associated with progressive brain injury and a higher risk of mortality, epilepsy, and permanent neurodevelopmental impairment. Therefore, early control of GCSE is pivotal for improving patients' outcomes.
A potential approach for early control of GCSE is the use of early ASM polytherapy. Ketamine is a promising option to be combined with standard ASMs for more rapid control of seizures. Ketamine has been used for decades for pediatric procedural analgosedation due to its excellent safety profile and wide therapeutic index. Ketamine works as a noncompetitive antagonist for N-methyl-D-aspartate (NMDA) receptors, which are progressively upregulated by way of receptor trafficking during ongoing seizure activity. Ketamine administration is associated with termination or attenuation of refractory SE (RSE) and super-refractory SE (SRSE). Multiple observational studies have reported the efficacy of ketamine in the pre-hospital emergency treatment of BZD-refractory status epilepticus. Furthermore, the recently published Ket-Mid study demonstrated that the ketamine-midazolam combination was more effective than midazolam alone in the initial treatment of pediatric GCSE. However, the value of combining ketamine with levetiracetam for the treatment of BZD-refractory status epilepticus has not been well investigated.
The present study (Ketamine and Levetiracetam as Second-line antiseizure medication for Status Epilepticus in Children, KLaSSEC) aims to investigate the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE. The findings could help earlier control of seizures and better clinical outcomes for children with status epilepticus
- Being tested
- Ketamine, Levetiracetam, Placebo
- Medical subject headings
- Status Epilepticus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Intravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes
LevetiracetamDrug
Intravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes
PlaceboDrug
Intravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes
| Study group | Role | What they receive |
|---|---|---|
| Ketamine + Levetiracetam | Experimental | Not described Receives: Drug: Ketamine; Drug: Levetiracetam |
| Placebo + Levetiracetam | Placebo comparator | Not described Receives: Drug: Levetiracetam; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with cessation of seizures at 20-minute
Number of participants with cessation of clinically evident seizures at 20-minute after starting study drug administration without endotracheal intubation or need for other antiseizure medications or anticonvulsant sedatives
Measured: 20 minutes
Secondary outcomes (10)
Number of participants with cessation of seizures at 5-minute
Number of participants with cessation of clinically evident seizures at 5-minute after starting study drug administration
Measured: 5 minutes
Number of participants with sustained cessation of seizures
Number of participants with sustained cessation of clinically evident seizures from 20-minute to 60-minute after study drug administration with improved responsiveness (verbal communication, obeying commands, or purposeful reaction to painful stimuli) and no endotracheal intubation or use of any additional antiseizure medications or anticonvulsant sedatives.
Measured: From 20 minutes to 60 minutes
Number of participants with recurrence of seizures
Number of participants with recurrence of clinically evident seizures after initial control
Measured: From 20 minutes to 4 hours
Number of participants underwent endotracheal intubation
Number of participants underwent endotracheal intubation at 60 minutes after starting study drug administration
Measured: 60 minutes
Number of participants with severe hypotension
Number of participants with severe hypotension at 60 minutes after starting study drug administration
Measured: 60 minutes
Number of participants with severe hypertension
Number of participants with severe hypertension at 60 minutes after starting study drug administration
Measured: 60 minutes
Number of participants with severe cardiac arrhythmia
Number of participants with severe cardiac arrhythmia at 60 minutes after starting study drug administration
Measured: 60 minutes
Number of participants with emergence reactions
Emergence reactions (hallucination, delirium, vivid dreams, blurred/double vision, hypersalivation) requiring benzodiazepines or other therapies within 4 hours after starting study drug administration
Measured: 4 hours
Number of participants admitted to Pediatric Intensive Care Unit
Number of participants with admitted to Pediatric intensive Care Unit at 24 hours after starting study drug administration
Measured: 24 hours
Mortality
All-cause mortality at 24 hours after starting study drug administration
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2025
- Study start2 Jul 2025
- Primary completion30 Jun 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalized Convulsive Status EpilepticusStudies of the same condition, open and under way.
- More trials run by Sohag UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sohag University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elsayed Abdelkreem, Sohag University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07046611
- Sponsor's protocol ID
- Soh-Med-25-6-2PD
- Acronym
- KLaSSEC
- Status last verified
- Jul 2025
- First submitted
- 20 Jun 2025
- Last updated
- 3 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Unidentified individual participant data will be available to qualifying researchers upon a reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Combined Ketamine and Levetiracetam as a Second-line Anti-seizure Medication for Generalized Convulsive Status Epilepticus in Children
- ClinicalTrials.gov ID
- NCT07046611
- Acronym / sponsor ID
- KLaSSEC / Soh-Med-25-6-2PD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Sohag UniversityUniversity, hospital or other
- Study start
- 2 Jul 2025 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 1 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
About 40% of children with generalized convulsive status epilepticus (GCSE) are not terminated by first-line benzodiazepines (BDZs), and approximately 50% of BDZ-refractory GCSE are not controlled by second-line antiseizure medications. This study investigates the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE.
Detailed description
Generalized convulsive status epilepticus (GCSE) is the most common pediatric neurological emergency. Benzodiazepines (BDZs) are the recommended first-line anti-seizure medication (ASM) for GCSE, but they fail to halt seizures in about 40% of cases. Moreover, approximately 50% of BDZ-refractory GCSE are not terminated by second-line ASMs, including levetiracetam, valproate, and phenytoin. Continuous GCSE for a longer duration is associated with progressive brain injury and a higher risk of mortality, epilepsy, and permanent neurodevelopmental impairment. Therefore, early control of GCSE is pivotal for improving patients' outcomes.
A potential approach for early control of GCSE is the use of early ASM polytherapy. Ketamine is a promising option to be combined with standard ASMs for more rapid control of seizures. Ketamine has been used for decades for pediatric procedural analgosedation due to its excellent safety profile and wide therapeutic index. Ketamine works as a noncompetitive antagonist for N-methyl-D-aspartate (NMDA) receptors, which are progressively upregulated by way of receptor trafficking during ongoing seizure activity. Ketamine administration is associated with termination or attenuation of refractory SE (RSE) and super-refractory SE (SRSE). Multiple observational studies have reported the efficacy of ketamine in the pre-hospital emergency treatment of BZD-refractory status epilepticus. Furthermore, the recently published Ket-Mid study demonstrated that the ketamine-midazolam combination was more effective than midazolam alone in the initial treatment of pediatric GCSE. However, the value of combining ketamine with levetiracetam for the treatment of BZD-refractory status epilepticus has not been well investigated.
The present study (Ketamine and Levetiracetam as Second-line antiseizure medication for Status Epilepticus in Children, KLaSSEC) aims to investigate the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE. The findings could help earlier control of seizures and better clinical outcomes for children with status epilepticus
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine + Levetiracetam | Experimental | Drug: Ketamine, Drug: Levetiracetam |
| Placebo + Levetiracetam | Placebo comparator | Drug: Levetiracetam, Drug: Placebo |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age from 1 year to 16 years.
- Generalized convulsive status epilepticus (GCSE), defined as clinically observed generalized tonic-clonic convulsions that continue or recur without complete regaining of consciousness in between for longer than 5 minutes.
- Benzodiazepine-refractory, defined as continuous or recurrent GCSE in the emergency room after receiving an adequate benzodiazepine dose, with the last dose administered within 5 to 30 minutes.
Key exclusion criteria (8 listed)
- Failure to obtain informed consent.
- Prior treatment with antiseizure medication or anticonvulsant sedatives other than benzodiazepines for the presenting GCSE episode.
- Endotracheal intubation before enrollment.
- Acute traumatic brain injury.
- Cardiac arrest/post-anoxic seizures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineIntravenous ketamine (5 mg/ml concentration) 2 mg/kg (max 90 mg) over 2 minutes | Drug | Ketamine + Levetiracetam |
| LevetiracetamIntravenous levetiracetam (50 mg/ml concentration) 60 mg/kg (max 4500 mg) over 5 minutes | Drug | Ketamine + Levetiracetam, Placebo + Levetiracetam |
| PlaceboIntravenous isotonic saline 0.4 mL/kg (maximum 18 mL) over 2 minutes | Drug | Placebo + Levetiracetam |
Primary outcome
Number of participants with cessation of seizures at 20-minute
Time frame: 20 minutes
Number of participants with cessation of clinically evident seizures at 20-minute after starting study drug administration without endotracheal intubation or need for other antiseizure medications or anticonvulsant sedatives
10 secondary outcomes
Number of participants with cessation of seizures at 5-minute
Time frame: 5 minutes
Number of participants with sustained cessation of seizures
Time frame: From 20 minutes to 60 minutes
Number of participants with recurrence of seizures
Time frame: From 20 minutes to 4 hours
Number of participants underwent endotracheal intubation
Time frame: 60 minutes
Number of participants with severe hypotension
Time frame: 60 minutes
Number of participants with severe hypertension
Time frame: 60 minutes
Number of participants with severe cardiac arrhythmia
Time frame: 60 minutes
Number of participants with emergence reactions
Time frame: 4 hours
Number of participants admitted to Pediatric Intensive Care Unit
Time frame: 24 hours
Mortality
Time frame: 24 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Individual participant dataSharing planned: No. Unidentified individual participant data will be available to qualifying researchers upon a reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ketamine and Levetiracetam in people with 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 3 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 3 Jul 2025. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elsayed Abdelkreem, MD, PhD (1114232126 ext. +20, d.elsayedmohammed@med.sohag.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with cessation of seizures at 20-minute (time frame: 20 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jul 2025.