| CTRI Number |
CTRI/2023/10/058272 [Registered on: 04/10/2023] Trial Registered Prospectively |
| Last Modified On: |
14/06/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Usefulness of levetiracetam in improving chances of recovery in patients of acute stroke with abnormal EEG |
|
Scientific Title of Study
|
Efficacy of prophylactic Levetiracetam in improving the functional outcome in acute stroke with epileptiform activity (LEVAS-EA): A randomized double blind, placebo controlled, pilot study |
| Trial Acronym |
LEVAS-EA |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Swapan Gupta |
| Designation |
Associate Professor |
| Affiliation |
GB Pant Institute of Post Graduate Medical Education and Research, New Delhi |
| Address |
Department of Neurology, Maulana Azad Medical College and
associated GB Pant Institute of Post Graduate Medical Education
and Research, New Delhi
New Delhi
DELHI
110002
India |
| Phone |
9718599351 |
| Fax |
|
| Email |
gupta.swapan@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Swapan Gupta |
| Designation |
Associate Professor |
| Affiliation |
GB Pant Institute of Post Graduate Medical Education and Research, New Delhi |
| Address |
Department of Neurology, Maulana Azad Medical College and
associated GB Pant Institute of Post Graduate Medical Education
and Research, New Delhi
New Delhi
DELHI
110002
India |
| Phone |
9718599351 |
| Fax |
|
| Email |
gupta.swapan@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Pranay Gupta |
| Designation |
Senior Resident |
| Affiliation |
GB Pant Institute of Post Graduate Medical Education and Research, New Delhi |
| Address |
Department of Neurology, Maulana Azad Medical College and
associated GB Pant Institute of Post Graduate Medical Education
and Research, New Delhi
New Delhi
DELHI
110002
India |
| Phone |
8879519859 |
| Fax |
|
| Email |
pranayag10@gmail.com |
|
|
Source of Monetary or Material Support
|
| GB Pant Institute of Post Graduate Medical Education and Research, New Delhi 110002 |
|
|
Primary Sponsor
|
| Name |
GB Pant Institute of Post Graduate Medical Education and Research, New Delhi 110002 |
| Address |
Jawahar Lal Nehru Marg, New Delhi-110002 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Swapan Gupta |
GB Pant Institute of Post Graduate Medical Education and Research |
Room no 503,Neurology
department,5th floor,
academic block.
Jawaharlal Nehru Marg
New Delhi
DELHI
New Delhi
DELHI |
9718599351
gupta.swapan@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethical Committee, MAMC |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G819||Hemiplegia, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Tablet Levetiracetam |
Levetiracetam will be started in the intervention group within 24 hours of randomisation in the dose of 20 mg/kg in two divided doses and gradually increased by 10 mg/kg every 3 days to a maintenance dose of 40 mg/kg/day in two divided doses. This will continue for the entire study period and after 12 weeks, the trial medication will be tapered off by 250 mg each 3 days and eventually discontinued. If patient reports intolerable side effects in which case the drug dose will be decreased to the tolerable level, but not below 20 mg/kg/day. If patient does not tolerate the lowest permissible dose, it will be stopped and the side effects will be managed free of cost as per standard of care. Patient will be followed up on day 7,30,60 and final follow up at 90 days. If patient has a seizure in the follow up period, another anti-seizure medication (ASM) will be added as per Post stroke seizure standard guidelines. |
| Comparator Agent |
Tablet placebo |
Placebo will be started in the comparator group within 24 hours of randomisation in the dose of 20 mg/kg in form of same 500 mg tablets which will be increased by 10 mg/kg every 3 days to a maintenance dose of 40 mg/kg/day in two divided doses. This will continue for the entire study period and after 12 weeks, the trial medication will be tapered off by 250 mg each 3 days and eventually discontinued. If patient reports intolerable side effects in which case the drug dose will be decreased to the tolerable level, but not below 20 mg/kg/day. If patient does not tolerate the lowest permissible dose, it will be stopped and the side effects will be managed free of cost as per standard of care. If patient has a seizure in the follow up period, another anti-seizure medication (ASM) will be added as per Post stroke seizure standard guidelines. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Age ≥ 18 years
2. Patients with Acute stroke with epileptiform activity without overt seizures
3. mRS ≥ 2
4. NIHSS ≥ 6 |
|
| ExclusionCriteria |
| Details |
1. Ischaemic Stroke with NIHSS > 25 at presentation
2. Intracerebral haemorrhage with GCS < 8 at presentation
3. Infratentorial Stroke
4. Subarachnoid haemorrhage
5. Subdural haemorrhage
6. Extradural haemorrhage
7. Primary Intraventricular Haemorrhage
8. Intracerebral haemorrhage known or suspected by study investigator to be secondary to trauma, vascular malformation
9. Stroke with seizure onset
10. Severe medical or surgical illness
11. Premorbid MRS >2
12. Patients with Dementia
13. Patients with intra-axial or extra-axial tumours
14. Already on antiseizure medication due to epilepsy or any reason
15. Previous history of severe depression or psychotic disorder
16. Pregnancy or breastfeeding
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Case Record Numbers |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Change in mRS (modified Rankin Scale) compared with baseline |
90 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
A. Seizure related
A.1) Occurrence of first late onset seizure
A.2) Time to occurrence of first late onset seizure
A.3) Seizure severity of first late onset seizure
A.4) Change in epileptiform activity
B. Functional outcome related
B.1) Change in Neurocognitive function (Montreal Cognitive Assessment) compared with baseline
B.2) Change in NIHSS (National Institute of Health Stroke Scale) compared with baseline
B.3) Handicap score (Barthel index) compared with baseline
B.4) Quality of life (Stroke Specific Quality of Life) compared with baseline
C. The occurrence of side effects of the trial medication (Side-Effects of Antiepileptic Drugs score) |
90 days |
|
|
Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "60"
Final Enrollment numbers achieved (India)="60" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
06/10/2023 |
| Date of Study Completion (India) |
28/05/2025 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Informed Consent Form
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - For individual participant data meta-analysis.
- By what mechanism will data be made available?
Response - Proposals should be directed to [gupta.swapan@gmail.com].
- For how long will this data be available start date provided 20-03-2026 and end date provided 19-03-2029?
Response - Beginning 9 months and ending 36 months following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
Presence of epileptiform activity in acute stroke patients has been linked to poorer functional outcome. Levetiracetam (LEV), an antiseizure medication with a good safety profile is known to have anti epileptogenic and neuroprotective effect. So therefore levetiracetam,
by virtue of its both antiepileptogenic
and neuroprotective effects, would be beneficial in improving the functional outcome patients of acute stroke
with presence of epileptiform activity without overt seizures
We therefor aim to conduct a double-blind, placebo-controlled study for its role in acute stroke patients with epileptiform activity
All patients fulfilling inclusion and exclusion criteria will be evaluated as per a detailed structured proforma. This study will consist of a double-blind treatment phase (DBTP) for 12 weeks
This study tests 1 hypotheses, namely Levetiracetam 40mg/kg is superior to placebo 40 mg/kg in improving the functional outcome of acute stroke patients without epileptiform activity. So, a planned enrolment of 30 patients per group (Levetiracetam and placebo) shall be done for 2 groups
Levetiracetam will be started in the
intervention group within 24 hours of randomisation in the dose of 20 mg/kg in
two divided doses and gradually increased by 10 mg/kg every 3 days to a
maintenance dose of 40 mg/kg/day in two divided doses. This will continue for
the entire study period and after 12 weeks, the trial medication will be
tapered off by 250 mg each 3 days and eventually discontinued. If patient
reports intolerable side effects in which case the drug dose will be decreased
to the tolerable level, but not below 20 mg/kg/day. If patient does not
tolerate the lowest permissible dose, it will be stopped and the side effects
will be managed free of cost as per standard of care. If patient has a seizure
in the follow up period, another anti-seizure medication (ASM) will be added as
per Post stroke seizure standard guidelines. Compliance will be
assured by medication count.
Patient will be followed up after 7
days, 30 days and 60 days to enquire about history of any possible epileptic
seizures & any drug related side effects which will be assessed by SIDEAD
questionnaire. Seizure severity will be assessed by either focal
or generalised event. The follow up will be done on a OPD basis or
telephonically if OPD follow up not possible.
Final follow up will be done at 90 days. Parameters
like patient mRS, seizure occurrence, adverse effects of ASM (SIDEAD), NIHSS,
MoCA, BI, GCS, SS-QOL and epileptiform activity on EEG will be recorded by
direct face to face patient interaction. |