Comparison of the Efficacy of Phenytoin and Levetiracetam in Children with Benzodiazepine-Resistant Status Epilepticus: A Randomized Controlled Clinical Trial
Comparison of the efficacy of Phenytoin and Levetiracetam in children with benzodiazepine-resistant status epilepticus.
Design
Study Type: Randomized Controlled Trial (RCT).
Randomization: Block randomization using blocks of 2, 4, and 8.
Blinding: Double-blinding is not feasible due to differences in infusion durations.
Settings and conduct
Location: Mofid Hospital, Tehran.
Procedure: Patients with persistent status epilepticus after two doses of benzodiazepines are randomized into one of the two treatment groups
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
Boys or girls aged 6 months to 17 years and 11 months.
Benzodiazepine-resistant status epilepticus (BRSE) after two doses of benzodiazepines.
Exclusion Criteria:
Known or suspected pregnancy.
Allergy or contraindication to Levetiracetam or Phenytoin.
Known renal failure (renal function below 50% of the expected for age).
Prior administration of a second-line antiepileptic drug before emergency department admission.
Seizures following head trauma.
Underlying heart disease.
Intervention groups
Group 1: Intravenous Levetiracetam at a dose of 40 mg/kg over 5 minutes (maximum dose 2.5 g).
Group 2: Intravenous Phenytoin at a dose of 20 mg/kg over at least 20 minutes (maximum dose 2 g at a maximum infusion rate of 1 mg/kg/min).
Main outcome variables
Primary Outcome: Time from the start of drug infusion to the cessation of all observable seizure activity.
Secondary Outcomes: Requirement for additional antiepileptic drugs, ICU admission, and occurrence of serious adverse events (death, respiratory depression, cardiovascular instability).
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20241019063425N1
Registration date:2025-01-02, 1403/10/13
Registration timing:registered_while_recruiting
Last update:2025-01-02, 1403/10/13
Update count:0
Registration date
2025-01-02, 1403/10/13
Registrant information
Name
Seyed Amin Jazayeri
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2264 3689
Email address
aminjaz430@yahoo.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2024-12-30, 1403/10/10
Expected recruitment end date
2025-12-22, 1404/10/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of the Efficacy of Phenytoin and Levetiracetam in Children with Benzodiazepine-Resistant Status Epilepticus: A Randomized Controlled Clinical Trial
Public title
Trial of Phenytoin and Levetiracetam in Children with Resistant Status Epilepticus
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Boys or girls aged 6 months to 17 years and 11 months
The patient has received two consecutive doses of first-line treatment but continues to experience ongoing status epilepticus.
Exclusion criteria:
Patients with known or suspected pregnancy
Patients with a known contraindication or allergy to Levetiracetam or Phenytoin
Patients with known renal failure (patients undergoing hemodialysis or with renal function below 50% of the expected for their age)
Prior administration of a second-line antiepileptic drug before admission to the emergency department
Seizures following head trauma
Individuals with underlying heart disease
Age
From 6 months old to 18 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
128
Randomization (investigator's opinion)
Randomized
Randomization description
Double-blinding is not feasible due to the difference in the infusion durations of these two drugs. A random sequence prepared in advance, using blocks of 2, 4, and 8, is generated through simple randomization and used to assign each patient to a treatment. Patients are entered into the random sequence based on the order of their arrival.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
The specialized committee of ethics in biomedical research
Street address
Shahid Beheshti University of Medical Sciences and Health Services, University Headquarters, Building No. 2, 6th Floor, Arabi Street, Yemen Street, Shahid Chamran Highway, Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1985717444
Approval date
2024-10-12, 1403/07/21
Ethics committee reference number
IR.SBMU.MSP.REC.1403.390
Health conditions studied
1
Description of health condition studied
status epilepticus
ICD-10 code
G40.301
ICD-10 code description
refractory status epilepticus
Primary outcomes
1
Description
The time from the start of drug injection to the cessation of all visible signs of seizure activity, which is defined as the cessation of all rhythmic seizure activity.
Timepoint
From the time of drug injection to the end of epileptic status
Method of measurement
using a stopwatch by the therapist
Secondary outcomes
1
Description
The need for tertiary anticonvulsants to manage seizures after second-line therapy
Timepoint
After failure to respond to second-line therapy
Method of measurement
The number of patients who needed third-line treatment is recorded in each group
Intervention groups
1
Description
Intervention group: Levetiracetam is administered over 5 minutes at a dose of 40 mg/kg, with a maximum dose of 2.5 grams. Following the initiation of injection, the patient is monitored by the resident for the cessation of SE symptoms, and when possible, a video recording is made to document the exact time SE ends. During SE treatment, the APLS algorithm is always followed, and emergency measures (e.g., intubation) are performed if necessary.
Category
Treatment - Drugs
2
Description
Intervention group: Phenytoin is administered over a minimum of 20 minutes at a dose of 20 mg/kg, with a maximum dose of 2 grams and an infusion rate of no more than 1 mg/kg/min. If one medication does not result in a response, the patient is reevaluated, and the persistence of SE is confirmed before initiating another medication. For instance, if the patient does not respond to phenytoin, levetiracetam will be started. The response to phenytoin is assessed up to 25 minutes after initiation, while the response to levetiracetam is evaluated up to 10 minutes after the start of infusion. Patients' outcomes are documented accordingly.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Mofid's children hospital
Full name of responsible person
Farzad Ahmad Abadi
Street address
Mofid children hospital, Shariati Street, above Hosseinieh Ershad, Tehran, Tehran Province, Iran.
City
Tehran
Province
Tehran
Postal code
15468 15514
Phone
+98 21 22227
Email
farzadpt@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Farzad Ahmadabadi
Street address
Shahid Shahriari Square, Shahid Shahriari Square, Shahid Beheshti University, Shahid Beheshti University, Building No. 2, Faculty of Health, Neuroscience Research Center (3rd and 4th floor), Evin, Tehran, Iran
City
tehran
Province
Tehran
Postal code
1983969367
Phone
+98 21 2242 9766
Email
nrciran@sbmu.ac.ir
Web page address
https://nrc.sbmu.ac.ir/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Shahid Beheshti University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Farzad Ahmadabadi
Position
Professor of Shahid Beheshti University of Medical Sciences
Latest degree
Subspecialist
Other areas of specialty/work
Neuroscience
Street address
Mofid Hospital, Shariati Street, Tehran
City
Tehran
Province
Tehran
Postal code
196151178
Phone
+98 21 2242 9768
Email
farzadpt@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Farzad Ahmadabadi
Position
Professor of Shahid Beheshti University of Medical Sciences
Latest degree
Subspecialist
Other areas of specialty/work
Neuroscience
Street address
Mofid Hospital, Shariati Street, Tehran
City
Tehran
Province
Tehran
Postal code
196151178
Phone
+98 21 2242 9768
Email
farzadpt@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Farzad Ahmadabadi
Position
Professor of Shahid Beheshti University of Medical Sciences
Latest degree
Subspecialist
Other areas of specialty/work
Neuroscience
Street address
Mofid Hospital, Shariati Street, Tehran
City
Tehran
Province
Tehran
Postal code
196151178
Phone
+98 21 2242 9768
Email
farzadpt@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD