| CTRI Number |
CTRI/2024/11/076684 [Registered on: 12/11/2024] Trial Registered Prospectively |
| Last Modified On: |
02/02/2026 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A clinical trial to understand the role of anti-epileptic therapy (medications to treat seizures) in the neurological outcomes of children with high intracranial pressures (high pressure within the skull/ cranial cavity). |
|
Scientific Title of Study
|
Role of Prophylactic Antiepileptic Therapy in the management of Clinically Diagnosed Raised Intracranial Pressures in Children: A Randomised Clinical Trial |
| Trial Acronym |
PAIP Study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NOT APLLICABLE |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
JOVIN CHRIS ANTONY |
| Designation |
Senior Resident |
| Affiliation |
All India Institute of Medical Sciences, Raipur |
| Address |
Senior Resident,
Division of Pediatric Emergency Medicine,
Dept. of Pediatrics,
All India Institute of Medical Sciences Raipur,
Tatibandh, G. E Road, Raipur
Chhattisgarh, 492099
Raipur
CHHATTISGARH
492099
India |
| Phone |
9944197619 |
| Fax |
|
| Email |
jovinchris@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Tushar Bharat Jagzape |
| Designation |
Professor |
| Affiliation |
All India Institute of Medical Sciences, Raipur |
| Address |
Dept. of Pediatrics,
All India Institute of Medical Sciences Raipur,
Tatibandh, G. E Road, Raipur
Chhattisgarh, 492099
Raipur
CHHATTISGARH
492099
India |
| Phone |
9421783796 |
| Fax |
|
| Email |
tusharjagzape@aiimsraipur.edu.in |
|
Details of Contact Person
Public Query
|
| Name |
JOVIN CHRIS ANTONY |
| Designation |
Senior Resident |
| Affiliation |
All India Institute of Medical Sciences, Raipur |
| Address |
Senior Resident,
Division of Pediatric Emergency Medicine,
Dept. of Pediatrics,
All India Institute of Medical Sciences Raipur,
Tatibandh, G. E Road, Raipur
Chhattisgarh, 492099
Raipur
CHHATTISGARH
492099
India |
| Phone |
9944197619 |
| Fax |
|
| Email |
jovinchris@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences (AIIMS) Raipur
Complete official address:
All India Institute of Medical Sciences Raipur, G.E Road, Tatibandh, Raipur, Chhattisgarh, India, PIN: 492099 |
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences Raipur |
| Address |
Division of Pediatric Emergency Medicine,
Dept. of Pediatrics,
AIIMS Raipur,
Tatibandh, G. E Road, Raipur Chhattisgarh, 492099 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Dr Anil Kumar Goel |
Professor & HOD,
Dept. of Pediatrics,
AIIMS Raipur,
Tatibandh, G. E Road, Raipur,
Chhattisgarh, 492099 |
| Dr Tushar Bharat Jagzape |
Professor,
Dept. of Pediatrics,
AIIMS Raipur,
Tatibandh, G. E Road, Raipur,
Chhattisgarh, 492099 |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Jovin Chris Antony |
All India Institute of Medical Sciences, Raipur |
Dept. of Pediatrics,
424, D block, AIIMS Raipur,
Tatibandh, G. E Road, Raipur,
Chhattisgarh, 492099
Raipur
CHHATTISGARH |
09944197619
jovinchris@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| IEC, AIIMS Raipur |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G988||Other disorders of nervous system, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Phenytoin, Levetiracetam |
There are 2 intervention arms/groups and 1 control arm/group (total 3 groups/arms) in this study. The intervention arm uses prophylactic AEDs - one arm will receive Levetiracetam and the other will get Phenytoin. The control arm will be given only placebo. The study involves using prophylactic AEDs (Phenytoin and Levetiracetam) in clinically diagnosed raised intracranial pressures in children 1 month -14 years of age, presenting to the Pediatric Dept (Emergency/ PICU/ Ward) of AIIMS Raipur, so as to understand the effect in reducing neurological morbidity. As of now, prophylactic use of AEDs for intracranial hypertension as a neuroprotective measure is not yet the standard practice in the scientific literature. And till date, the practice of use of AEDs in raised ICP is still varying across practitioners and institutes. Some routinely use it and some do not. Hence, this study is to throw light into this grey area of medical practice. For the intervention arm 1, inj. Levetiracetam will be loaded at 20 mg/kg (maximum dose – 1500 mg) in 20 ml of NS over 20 minutes and maintained at 20 mg/kg/day at 12 hourly intervals and then, switched to the same oral therapy as clinically warranted. Oral maintenance therapy will be stopped after 7 days. In case of recurrence of seizures, the dosage can be increased to 60 mg/kg/day (maximum dose of 3000 mg/day) as per the standard treatment guidelines. For the intervention arm 2, inj. Phenytoin will be loaded at 20 mg/kg (maximum dose 1500 mg) in 20 ml of NS over 20 minutes, under cardiac monitoring, with a rate of not more than 1 mg/kg/mt and shall be maintained at 5 mg/kg/day at 12 hourly intervals, and then, switched to the same oral therapy as clinically warranted. Oral maintenance therapy will be stopped after 7 days. In case of recurrence of seizures, the dosage can be increased to 8 mg/kg/day (maximum dose of 600 mg/day) as per the standard treatment guidelines. |
| Comparator Agent |
Placebo (Inj. 0.9% Normal Saline and B complex tablet) |
The control/ placebo arm will be given 10 ml of 0.9% normal saline (NS) slow IV push initially followed by twice daily at 12 hr intervals for first 48 hours. Then, for the next 5 days (till 1 week from initial presentation), child will be given B complex tablets twice daily. This group will also be observed for seizures; if seizures occur, then, child will be treated with either Levetiracetam or Phenytoin as per the above norms as decided by the treating physician and included in the intention to treat analysis. |
|
|
Inclusion Criteria
|
| Age From |
1.00 Month(s) |
| Age To |
14.00 Year(s) |
| Gender |
Both |
| Details |
1. Children presenting to the Pediatric Emergency Medicine Unit with clinical findings consistent with raised ICP and not had h/o seizures.
2. Children already loaded elsewhere prophylactically, with appropriate standard dosing (as used in the study) of Levetiracetam/ Phenytoin and referred here; with findings consistent with raised ICP in PEM shall also be included in the concerned anti-epileptic drug arm and observed further with the maintenance dose.
|
|
| ExclusionCriteria |
| Details |
1. Known seizure disorder/ epilepsy on regular antiepileptic therapy (Those children meeting the criteria, with only febrile seizures on intermittent AED prophylaxis, will not be excluded).
2. Children with ICP who already had seizures.
3. Post cardiac arrest/ history of CPR.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
1. Incidence of occurrence of acute symptomatic seizures (ASS; including Non-Convulsive Status Epilepticus) in 48 hours from admission within the 3 groups.
2. Incidence of 48 hours mortality & reduction of 48 hours predicted mortality index from baseline prediction at admission based on PRISM 3 scores in the 3 study groups.
|
48 hours |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. Seizure recurrence/ occurrence after 48 hours till discharge from the hospital/ during 1 month follow up period in 3 groups
2. Outcome analysis to be done at 7 days and 1 month in 3 study groups by means of survival analysis.
3. Efficacy of Phenytoin v/s Levetiracetam in reducing the mortality at 48 hours and morbidity patterns at 48 hours & 7 days/ till discharge from the hospital whichever is earlier, as subgroup analysis in the treatment groups.
4. Occurrence of potential side effects of the AEDs and the impact of the same with morbidity/ hospital stay in the treatment groups.
5. Rate of dose increment events among both treatment groups.
|
1 month |
|
|
Target Sample Size
|
Total Sample Size="90"
Sample Size from India="90"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
17/11/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The
children between 1-month to <14 years of age, who present to the Pediatric
emergency Medicine Unit (PEM), AIIMS Raipur with symptomatology and clinical
assessment at the end of triaging/ primary and secondary assessments suggestive
of raised ICP, with parents willing for consent for the study and those fitting
into the inclusion criteria would be enrolled for the study. Those with any of the exclusion criteria being met, would be excluded. Computer-generated
block randomization with block size 6{2 for phenytoin treatment arm – denoted
with letter P, 2 for Levetiracetam treatment arm – denoted with letter L
and 2 for placebo (Normal saline) arm – denoted with letter N} will be used
and an envelope concealment method shall be employed. At admission, sealed
envelopes can be taken from the allocation box, kept ready in prior in the
nursing desk and the researcher allocates the patient into one of the three
arms and loads/ does not load with antiepileptic therapy as needed for the
allocation. This is an open labelled study and there is no blinding. The routine management for raised ICP shall be continued similarly as per standard
treatment guidelines and as warranted by the clinical state, for both groups.
Baseline
data and demography will be collected, and patient will be followed up meticulously
for various outcomes of interest as listed above at 48 hours, 7 days/ till
discharge. In the event of occurrence of seizures in the control group, antiepileptic
medication – Levetiracetam/ Phenytoin shall be loaded as per the physician’s
discretion, and they shall be treated as per institutional protocol for ethical
reasons. Intention to treat analysis shall be employed for them too. The
nursing staff in PEM will be taught and informed about giving drugs P, L and N in
the groups concerned and shall be made readily available in the ward stock. If
the child survives up to discharge, will be followed up till 30 days (1 month) via
phone call and details shall be collected. Data obtained will be entered in Excel
sheets. After the study is complete, analysis of the data will be performed
using intention to treat process using latest SPSS version. |