Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06067412 |
| Other study ID # |
184-86 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2022 |
| Est. completion date |
January 31, 2023 |
Study information
| Verified date |
September 2023 |
| Source |
Shaheed Zulfiqar Ali Bhutto Medical University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Status epilepticus is the second most common neurologic emergency in children. Morbidity and
mortality are considerable; thus, timely termination of convulsive status epilepticus is the
primary goal of management to avoid these risks Our objective was to compare the efficacy of
phenytoin and Levetiracetam in status epilepticus in children.
This study was done in the pediatric emergency department of Children Hospital Faisalabad.
A total of 70 patients were randomly allocated to one of the groups by a computer-generated
random number table according to their admission in an emergency. Children in group A were
given levetiracetam. Children in group B were given I/V phenytoin. For both groups if
seizures recurred after the first loading dose an additional 10mg/kg of the same drug was
given over 10 minutes.
The patients were monitored to see whether there was any recurrence of seizure activity in
the subsequent 24 hours. Seizure control was defined as the absence of seizure within 24
hours after the initial loading of the drug.
Description:
OPERATIONAL DEFINITION
Status Epilepticus:
It is defined as continuous seizure activity or recurrent seizure activity without regaining
of consciousness lasting for more than 5 minutes.
Efficacy:
Efficacy means control of seizures without supplemental aid of either medication or no
recurrence with in twenty-four hours.
HYPOTHESIS H0: There is no significant difference between efficacy of Phenytoin and
Levetiracetam in Status Epilepticus in Children H1: There is significant difference between
efficacy of Phenytoin and Levetiracetam in Status Epilepticus in Children.
MATERIAL AND METHODS
STUDY DESIGN:
Randomized Controlled Trial (RCT). SETTING This study was done in pediatric emergency
department of Children Hospital Faisalabad.
DURATION OF STUDY The duration of study was six months after the approval of synopsis From:
1/8/2022 to 31/1/2023
SAMPLE SIZE:
By using WHO sample size calculator for two proportions:
p1=96%7, p2=59.6%7 power of study = 90% Level of significance = 5% Sample Size = 70 (35 in
each group) SAMPLING TECHNIQUE Nonprobability consecutive sampling
DATA COLLECTION PROCEDURE After approval from IRB, patient fulfilling the inclusion criteria
were enrolled. Written informed consent was taken and data was collected through predesigned
Performa in emergency of Children Hospital Faisalabad. The patients were randomly allocated
to one of the group by computer generated random number table according to their admission in
emergency. After taking full care of Airway and Breathing I/V line was established children
who presented with active seizures were given Diazepam at a dose of 0.1 mg /kg I/V slowly
stat followed by I/V levetiracetam or phenytoin according to group allocation. Children with
recent history of status epilepticus but now present with no active seizures were given only
I/V levetiracetam or phenytoin.
Children in group A was given levetiracetam at a dose of 30 mg/kg diluted in 50 ml of normal
saline in 15 minutes followed by a maintenance dose of 30mg/kg/day divided in two doses 12
hours apart after initial loading dose. Children in group B was given I/V phenytoin at 20
mg/kg diluted in 50ml normal saline in 15 minutes followed by maintenance dose of 5 mg/kg/day
divided in two doses 12 hours apart. For both groups if seizures recurred after the first
loading dose an additional 10mg/kg of the same drug was given over 10 minutes. If seizures
recurred, the patients were loaded with sodium valporate 30 mg/kg diluted in 50 ml normal
saline in 15 minutes.
The parameters which include level of consciousness (GCS), heart rate, respiratory rate,
blood pressure and oxygen saturation was noted first at the time of admission and then again
at 30 minutes, 1hour, 6hour, 12hour and 24 hours. The patients were monitored to see whether
there was any recurrence of seizure activity in subsequent 24 hours. Seizure control was
defined as the absence of seizure for 24 hours after the initial loading of the drug.
DATA ANALYSIS PROCEDURE:
Data was analyzed by SPSS V-25. Frequency and Percentage was calculated for all qualitative
variables like gender, type of seizures and efficacy. Mean ± Standard Deviation was
calculated for all quantitative variables like age and weight. Efficacy was compared by
applying chi-square test between two groups. Effect modifiers like age, gender, weight and
type of seizures were controlled by stratification. Post stratification chi-square test was
applied P ≤ 0.05 was taken as significant.
DISCUSSION In order to avoid neurologic and systemic disease, effective treatment of status
epilepticus is necessary. The prompt identification and complete cessation of seizures have
to be the overarching objectives of any therapy. In order for an anticonvulsant medication to
be successful in treating status epilepticus, it must be given intravenously. This allows for
the medication to be delivered to the brain more quickly while also reducing the likelihood
of major side effects on the nervous system. There is more than one medication available, and
each one has its own set of benefits and drawbacks.
There have been a number of studies published on the efficacy of both drugs but the data
showing the relative effect of both drugs is still insufficient. In Pakistan there were only
few researches showing efficacy of both drugs, this leads to the thought to conduct this
particular research in our hospital to compare their relative efficacy in order to improve
the seizure control time in our hospital and benefit patients with the best available drug.
Many randomized clinical trials clearly supports the use of benzodiazepine as the first line
treatment in status epilepticus.But, if the seizure control was not established than 2nd line
drugs phenytoin , levetiracetam and sodium valporate were used.There were mixed results in
terms of efficacies of both drugs .In one study, mean age was 4.09 years with male
predominance and most common type of seizures were generalized tonic clonic (74%).The seizure
control time in all 104 patients was within 40 minutes. Seizures were better controlled in
group 1 (levetiracetam 96%) as compared to group 2 (phenytoin 59.6%) in 1st 24 hours
(P=0.0001).
Numerous studies have shown that levetiracetam is a safer AED to give than phenytoin, despite
the fact that both medications are as effective in treating SE. This is the case despite the
fact that the two drugs have equivalent efficacies. The incidence of adverse effects
associated with the therapy with phenytoin was considerably higher than the incidence of
adverse effects associated with levetiracetam. The most prevalent adverse event was acute
hypotension.
When treating SE, another clinical investigation found that intravenous (IV) fosphenytoin was
linked with much more vasopressor use than levetiracetam. This was mostly owing to the
hypotension that was generated by the treatment.The danger of hypotension that is linked with
intravenous (IV) phenytoin and fosphenytoin might contribute to worse patient outcomes. This
is because maintaining cerebral blood perfusion is essential for helping to avoid neuronal
impairment in In addition, clinical trials have shown that administering phenytoin
intravenously might result in potentially deadly arrhythmias in the heart. Although at first
it was believed that phenytoin would lower the risk of cardiac toxicity, it now seems that
fosphenytoin also causes cardiac arrhythmias. On the other hand, levetiracetam has a less
severe adverse effect profile and shows signs of being well tolerated in a variety of patient
demographics when it comes to the treatment of SE.
In comparison to phenytoin, the pharmacokinetics of levetiracetam are more favorable, and it
is easier to administer. These are two of the many benefits of utilizing levetiracetam to
treat SE.Levetiracetam, in contrast to phenytoin, is not metabolized by the CYP450 enzyme
system in the liver. As a result, the likelihood of levetiracetam interacting negatively with
other medications that are processed by CYP450 is significantly reduced.
In addition, levetiracetam has a bioavailability that is close to one hundred percent and, in
contrast to phenytoin, it does not need to have its dosage closely monitored all the time.
Another benefit of levetiracetam is that it has linear pharmacokinetics and a wide
therapeutic index, both of which significantly lessen the likelihood that the medication
would cause adverse effects. It is essential to note that the administration of levetiracetam
is noticeably simpler and more expedient than that of phenytoin. In point of fact,
administering a loading dosage of intravenous phenytoin to a patient is a process that is
laborious and time-consuming, which further raises the potential for unintended side effects.
The effectiveness of the two medications in treating SE may be comparable; however,
levetiracetam is the antiepileptic drug (AED) that is safer and more well tolerated. As a
result, it ought to take the place of phenytoin and fosphenytoin for the purpose of ending
seizure activity in individuals who are resistant to benzodiazepines.
