SeizuresPhase 4E-PTSNCT07072624
Early Post-Traumatic Seizures Prevention Trial (E-PTS Trial)
A Phase 4 study testing Phenytoin and Levetiracetam in people with Seizures and Traumatic Brain Injuries, run by All India Institute of Medical Sciences, Jodhpur at 3 sites in India.
Trial summary
Rationale/gaps in existing knowledge: The prophylaxis for post-traumatic seizures (PTS) remains controversial due to a lack of class I evidence. Investigators plan to conduct a high-quality, prospective, multicentric, randomized study regarding seizure prophylaxis in traumatic brain injury (TBI) with phenytoin… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Seizures, Traumatic Brain Injuries, Traumatic Brain Injury (TBI) Patients
- What is being tested?
- Phenytoin and Levetiracetam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,260 participants
- Where
- 3 sitesIndia
- Study dates
- 23 Jul 2025to 15 Mar 2028
- Phase
- Phase 4
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of severe blunt TBI with GCS score less than 10.
- Patients with GCS of more than 10 in the presence of computed tomographic imaging findings consistent with brain injury: subarachnoid hemorrhage [SAH], subdural hematoma [SDH], epidural hematoma [EDH], intracerebral hemorrhage [ICH], or diffuse axonal injury [DAI], depressed skull fracture.
- Patients with penetrating injury.
Who cannot join
- Females of childbearing age with urine pregnancy test positive.
- Devastating brain injury with expected or confirmed brain death within 48 hours of hospital admission,
- Prehospital use of anticonvulsants
- Development of seizures before enrolment.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Dr Jaskaran Singh Gosal Associate Professor, MCh Neurosurgery contact
Dr Shoban Babu Varthya Associate Professor, MD Pharmacology contact
India3 sites, 3 recruiting
- Recruiting
Postgraduate Institute of Medical Education & Research
Chandigarh, Punjab, 160012
Dr Apinderpreet Singh Additional Professor, MCh Neurosurgery, +91 9914207338, apinderpreetsingh@gmail.com
Bikash Medhi, MD, +91 9815409652, drbikashus@yahoo.com
- Recruiting
AIIMS Jodhpur
Jodhpur, Rajasthan, 342005
Jaskaran S Gosal, MCh, +91 6283475891, jhsgosal_87@hotmail.com
Shoban B Varthya, MD, +91 8437726777, vartyasb@aiimsjodhpur.edu.in
- Recruiting
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Lucknow, Uttar Pradesh
Dr Kamlesh bhaisora Additional Professor, MCh Neurosurgery, +91 8004904457, drkamleshbhaisora@gmail.com
Raghavendra Lingaiah, MD, +91 9968868075, raghulingaiah@gmail.com
About this study
Official title: Assessing Phenytoin and Levetiracetam Efficacy, Cost-Effectiveness, and CYP2C9/SV2A Polymorphism in Early Post-Traumatic Seizures: A Multicentric Prospective Randomized Trial
Rationale/gaps in existing knowledge: The prophylaxis for post-traumatic seizures (PTS) remains controversial due to a lack of class I evidence. Investigators plan to conduct a high-quality, prospective, multicentric, randomized study regarding seizure prophylaxis in traumatic brain injury (TBI) with phenytoin, levetiracetam, and the placebo in three respective treatment groups, along with the effect of drug polymorphism on seizure occurrence.
Novelty: Literature is scarce regarding the ideal management of early PTS in traumatic brain injury (TBI), a major public health problem. Further, no study has evaluated the effect of genetic polymorphism on seizure occurrence in traumatic brain injury. This Multicentric study will be the first of its kind, not only in India but also globally.
Read more
Objectives: To evaluate the seizure incidence \& efficacy of the respective anti-epileptic drug in each treatment arm. Assessment of clinical \& functional outcomes, safety profile, and cost-effectiveness in each group. Effect of genetic polymorphisms on seizure incidence among study participants Methods: A Multicentric prospective randomized placebo-controlled double-blinded clinical trial is planned. After satisfying eligibility criteria and informed consent, TBI patients will be randomly allocated into three arms 'phenytoin arm', 'levetiracetam arm', and 'placebo'. Drug polymorphism will be analyzed in all the patients using quantitative real-time PCR.
Expected outcome: This study will provide high-quality evidence in PTS management and will establish the role of prophylactic anti-epileptics in PTS. This study also opens the plethora of undesignated roles of genetic polymorphism in the efficacy and safety of levetiracetam and phenytoin in traumatic brain injury patients.
- Being tested
- Phenytoin, Levetiracetam, Placebo
- Keywords
- Post Traumatic Seizures, Early Post Traumatic Seizures, Traumatic Brain Injury, Seizure Prophylaxis, Antiepileptic drugs, Phenytoin, Levetiracetam, Placebo, Genetic polymorphism, CYP2C9, SV2A, Randomized Controlled Trial, Cost-effectiveness, Multicentric Trial
- Medical subject headings
- Seizures, Brain Injuries, Traumatic, Epilepsy, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenytoinDrug
The Phenytoin group will be given a loading dose of phenytoin 20 mg/kg intravenously (maximum, 2 gm) at 50 mg per minute and then started on a maintenance dose (5-6 mg/kg/d, rounded to the nearest 100 mg, intravenously administered every 8 hours). The intravenous will be switched to oral once the patient is fit to take it orally or via Ryles tube. The oral dose would be a single 300 mg ER (extended-release) tablet per day. Both IV and/or oral doses of phenytoin will be given only for 1 week after head trauma. Patient= Patients with Traumatic brain injury as per eligibility criteria. Intervention= Phenytoin loading dose IV (20 mg/kg) followed by 100 mg IV TDS till patient accepts orally. Oral dose will be administered as a single 300 mg ER tablet per day. Both IV and oral phenytoin will be given for 1 week after traumatic brain injury and then stopped. Comparator= Matching Placebo
LevetiracetamDrug
The Levetiracetam group will receive 25-30 mg/kg/d in two divided doses (rounded to 750 mg, administered intravenously every 12 hourly). The intravenous dose will be switched to oral form once the patient is fit to take it orally or via Ryles tube. The oral dose would be two tablets of 750 mg ER (extended-release) levetiracetam daily. Both IV and/or oral doses of levetiracetam will be given only for 1 week after head trauma. Patient= Patients with Traumatic brain injury as per eligibility criteria. Intervention= Levetiracetam IV dosing will be 25-30 mg/Kg/d in 2 divided doses (rounded to 750 mg IV BD) followed by 2 tablets of 750 mg ER once patient fit to take orally or via Ryles tube. Comparator= Matching Placebo.
PlaceboDrug
The Placebo group will be administered normal saline intravenously of similar amount that of intervention group and matching placebo tablets orally (double dummy) once the patient is fit to take orally. Similar to the intervention group, both IV and oral placebo will be given till 1 week after traumatic brain injury.
| Study group | Role | What they receive |
|---|---|---|
| Phenytoin | Active comparator | Not described Receives: Drug: Phenytoin |
| Levetiracetam | Experimental | Not described Receives: Drug: Levetiracetam |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinical Seizure Within 7 Days Post-Traumatic Brain Injury in each of the three treatment groups.
A total of 1260 participants experiencing early clinical seizures (defined as any observable seizure activity occurring within 7 days post-trauma), as recorded by treating clinicians, and confirmed through clinical documentation, during the first 7 days of the study intervention period in each group (Phenytoin, Levetiracetam, Placebo).
Measured: 7 Days
Secondary outcomes (4)
Change in Glasgow Coma Scale scores from baseline at 7 days post-trauma, at 6 months, and 1 year in each treatment group.
Title: Functional and Neurological Status Assessed Using Glasgow Coma Scale (GCS).
Description:
Glasgow Coma Scale (GCS)-a clinical tool used to assess the level of consciousness in traumatic brain injury patients. Scores range from 3 to 15, where higher scores indicate better neurological function. The GCS differentiates between the severities of head injury by score ranges. A GCS of 13-15 indicates a mild head injury, 9-12 moderate and 3-8 severe.
Time Frame:
GCS: Day 1(Baseline), Day 3, Day 5, and Day 7, at discharge , at 6-month \& 1 year follow up.
Assessment Method:
GCS: Assessed by trained clinical staff daily using standard scoring protocol.
Measured: 7 Days , 6 Months & 1 year
Glasgow Outcome Scale scores at hospital discharge, 6-month, and 1-year follow-up in each treatment group.
Title: Functional and Neurological Status Assessed Using Glasgow Outcome Scale (GOS).
Description: Glasgow Outcome Scale (GOS) - a global outcome measure of functional recovery post-TBI. Scores range from 1 (death) to 5 (good recovery), where higher scores indicate better outcomes.
Time Frame: GOS: At hospital discharge and 6-month follow-up. Assessment method GOS: Assessed at discharge by clinical staff, and at 6 months and at 1 year via telephonic or in-person follow-up
Measured: At discharge, 6 months and 1 year
Incidence of early clinical seizures in participants, assessed in association with CYP2C9 and SV2A gene polymorphisms, using TaqMan allelic discrimination assay with quantitative real-time PCR (qPCR).
Title:
Association Between CYP2C9 and SV2A Genetic Polymorphisms and Early Seizure Incidence.
Description: Genotyping of CYP2C9 and SV2A polymorphisms will be performed using TaqMan allelic discrimination assay with quantitative real-time PCR. The incidence of early clinical seizures (defined as seizures occurring within 7 days post-trauma) will be compared across different genotype groups. The outcome will be reported as the number and proportion of participants with early seizures by genotype.
Time Frame: Within 7 days post-injury Unit of Measure: Number of participants with seizures per genotype group.
Measured: 7 days
Incremental Cost-Effectiveness Ratio (ICER) of Levetiracetam vs Phenytoin in Preventing Early Post-Traumatic Seizures using Markov chain Monte Carlo simulation.
Description: Cost-effectiveness within the trial will be assessed by calculating the Incremental Cost-Effectiveness Ratio (ICER), defined as the difference in direct medical costs per seizure complication prevented between the phenytoin and levetiracetam groups.
Cost data include direct medical cost like drug acquisition, hospital stay, ICU stay, investigations, and seizure-related interventions. Outcome data will include the number of patients with early clinical seizures (within 7 days).
Economic evaluation will be performed over a 1-year follow-up period using trial-based data. ICER values will be calculated along with 95% confidence intervals, and sensitivity analyses will be conducted using probabilistic approach. Long-term cost effectiveness will be modelled using Markov chain Monte Carlo simulation.
Time Frame: From randomization to 1-year post-injury follow-up. Measure Type: Cost-effectiveness ratio Unit of Measure: INR (₹) per seizure prevented
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start23 Jul 2025
- Primary completion15 Mar 2027 (estimated)
- Study completion15 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for SeizuresStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Jodhpur
- Sponsor type
- Other government
- Collaborators
- Indian Council of Medical Research, Post Graduate Institute of Medical Education and Research, Chandigarh, Sanjay Gandhi Postgraduate Institute of Medical Sciences
- Responsible party
- Principal investigator, Jaskaran Singh Gosal, All India Institute of Medical Sciences, Jodhpur
- Investigators
- Dr Apinderpreet Singh Additional Professor, MCh Neurosugery, Principal investigator, Post Graduate Institute of Medical Education and Research, ChandigarhDr Kamlesh Bhaisora Additional Professor, MCh Neurosugery, Principal investigator, Sanjay Gandhi Postgraduate Institute of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07072624
- Sponsor's protocol ID
- AIIMS/IEC/2024/4889
- Other IDs
- IIRPIG-2023-0001210
- Acronym
- E-PTS
- Status last verified
- Oct 2026
- First submitted
- 30 May 2025
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gupta V, Gupta K, Singh G, Kaushal S. An Analytical Study to Correlate Serum Levels of Levetiracetam with Clinical Course in Patients with Epilepsy. J Neurosci Rural Pract. 2016 Dec;7(Suppl 1):S31-S36. doi: 10.4103/0976-3147.196445.
PubMed 28163500Kousar S, Wafai ZA, Wani MA, Jan TR, Andrabi KI. Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance. Int J Clin Pharmacol Ther. 2015 Jul;53(7):504-16. doi: 10.5414/CP202112.
PubMed 25943175Chang WC, Hung SI, Carleton BC, Chung WH. An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):723-734. doi: 10.1080/17425255.2020.1780209. Epub 2020 Jul 16.
PubMed 32510242Dibbens LM, Hodgson BL, Helbig KL, Oliver KL, Mulley JC, Berkovic SF, Scheffer IE. Rare protein sequence variation in SV2A gene does not affect response to levetiracetam. Epilepsy Res. 2012 Sep;101(3):277-9. doi: 10.1016/j.eplepsyres.2012.04.007. Epub 2012 Apr 30.
PubMed 22551666Schivell AE, Mochida S, Kensel-Hammes P, Custer KL, Bajjalieh SM. SV2A and SV2C contain a unique synaptotagmin-binding site. Mol Cell Neurosci. 2005 May;29(1):56-64. doi: 10.1016/j.mcn.2004.12.011.
PubMed 15866046Jones KE, Puccio AM, Harshman KJ, Falcione B, Benedict N, Jankowitz BT, Stippler M, Fischer M, Sauber-Schatz EK, Fabio A, Darby JM, Okonkwo DO. Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury. Neurosurg Focus. 2008 Oct;25(4):E3. doi: 10.3171/FOC.2008.25.10.E3.
PubMed 18828701Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010 Apr;12(2):165-72. doi: 10.1007/s12028-009-9304-y.
PubMed 19898966Jarvie D, Mahmoud SH. Therapeutic Drug Monitoring of Levetiracetam in Select Populations. J Pharm Pharm Sci. 2018;21(1s):149s-176s. doi: 10.18433/jpps30081.
PubMed 30096051Cardona AF, Rojas L, Wills B, Bernal L, Ruiz-Patino A, Arrieta O, Hakim EJ, Hakim F, Mejia JA, Useche N, Bermudez S, Carranza H, Vargas C, Otero J, Mayor LC, Ortiz LD, Franco S, Ortiz C, Gil-Gil M, Balana C, Zatarain-Barron ZL. Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma. J Neurooncol. 2018 Jan;136(2):363-371. doi: 10.1007/s11060-017-2660-0. Epub 2017 Nov 25.
PubMed 29177594Dikmen SS, Temkin NR, Miller B, Machamer J, Winn HR. Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures. JAMA. 1991 Mar 13;265(10):1271-7.
PubMed 1995974Bhullar IS, Johnson D, Paul JP, Kerwin AJ, Tepas JJ 3rd, Frykberg ER. More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J Trauma Acute Care Surg. 2014 Jan;76(1):54-60; discussion 60-1. doi: 10.1097/TA.0b013e3182aafd15.
PubMed 24368357Young B, Rapp RP, Norton JA, Haack D, Tibbs PA, Bean JR. Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures. J Neurosurg. 1983 Feb;58(2):236-41. doi: 10.3171/jns.1983.58.2.0236.
PubMed 6848681Ferguson PL, Smith GM, Wannamaker BB, Thurman DJ, Pickelsimer EE, Selassie AW. A population-based study of risk of epilepsy after hospitalization for traumatic brain injury. Epilepsia. 2010 May;51(5):891-8. doi: 10.1111/j.1528-1167.2009.02384.x. Epub 2009 Oct 20.
PubMed 19845734Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998 Jan 1;338(1):20-4. doi: 10.1056/NEJM199801013380104.
PubMed 9414327Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/NEJM199008233230801.
PubMed 2115976
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Phenytoin and Levetiracetam Efficacy, Cost-Effectiveness, and CYP2C9/SV2A Polymorphism in Early Post-Traumatic Seizures: A Multicentric Prospective Randomized Trial
- ClinicalTrials.gov ID
- NCT07072624
- Acronym / sponsor ID
- E-PTS / AIIMS/IEC/2024/4889
- Keywords
- Post Traumatic Seizures, Early Post Traumatic Seizures, Traumatic Brain Injury, Seizure Prophylaxis, Antiepileptic drugs, Phenytoin, Levetiracetam, Placebo
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,260 participants (estimated)
- Lead sponsor
- All India Institute of Medical Sciences, JodhpurOther government
- Collaborators
- Indian Council of Medical Research, Post Graduate Institute of Medical Education and Research, Chandigarh, Sanjay Gandhi Postgraduate Institute of Medical Sciences
- Study start
- 23 Jul 2025 (actual)
- Primary completion
- 15 Mar 2027 (estimated)
- Study completion
- 15 Mar 2028 (estimated)
- First posted
- 18 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.
Rationale/gaps in existing knowledge: The prophylaxis for post-traumatic seizures (PTS) remains controversial due to a lack of class I evidence. Investigators plan to conduct a high-quality, prospective, multicentric, randomized study regarding seizure prophylaxis in traumatic brain injury (TBI) with phenytoin, levetiracetam, and the placebo in three respective treatment groups, along with the effect of drug polymorphism on seizure occurrence.
Novelty: Literature is scarce regarding the ideal management of early PTS in traumatic brain injury (TBI), a major public health problem. Further, no study has evaluated the effect of genetic polymorphism on seizure occurrence in traumatic brain injury. This Multicentric study will be the first of its kind, not only in India but also globally.
Objectives: To evaluate the seizure incidence \& efficacy of the respective anti-epileptic drug in each treatment arm. Assessment of clinical \& functional outcomes, safety profile, and cost-effectiveness in each group. Effect of genetic polymorphisms on seizure incidence among study participants Methods: A Multicentric prospective randomized placebo-controlled double-blinded clinical trial is planned. After satisfying eligibility criteria and informed consent, TBI patients will be randomly allocated into three arms 'phenytoin arm', 'levetiracetam arm', and 'placebo'. Drug polymorphism will be analyzed in all the patients using quantitative real-time PCR.
Expected outcome: This study will provide high-quality evidence in PTS management and will establish the role of prophylactic anti-epileptics in PTS. This study also opens the plethora of undesignated roles of genetic polymorphism in the efficacy and safety of levetiracetam and phenytoin in traumatic brain injury patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phenytoin | Active comparator | Drug: Phenytoin |
| Levetiracetam | Experimental | Drug: Levetiracetam |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients of severe blunt TBI with GCS score less than 10.
- Patients with GCS of more than 10 in the presence of computed tomographic imaging findings consistent with brain injury: subarachnoid hemorrhage [SAH], subdural hematoma [SDH], epidural hematoma [EDH], intracerebral hemorrhage [ICH], or diffuse axonal injury [DAI], depressed skull fracture.
- Patients with penetrating injury.
Key exclusion criteria (4 listed)
- Females of childbearing age with urine pregnancy test positive.
- Devastating brain injury with expected or confirmed brain death within 48 hours of hospital admission,
- Prehospital use of anticonvulsants
- Development of seizures before enrolment.
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 |
|---|---|---|
| PhenytoinThe Phenytoin group will be given a loading dose of phenytoin 20 mg/kg intravenously (maximum, 2 gm) at 50 mg per minute and then started on a maintenance dose (5-6 mg/kg/d, rounded to the nearest 100 mg, intravenously administered every 8 hours). The intravenous will be switched to oral once the patient is fit to take it orally or via Ryles tube. The oral dose would be a single 300 mg ER (extended-release) tablet per day. Both IV and/or oral doses of phenytoin will be given only for 1 week after head trauma. Patient= Patients with Traumatic brain injury as per eligibility criteria. Intervention= Phenytoin loading dose IV (20 mg/kg) followed by 100 mg IV TDS till patient accepts orally. Oral dose will be administered as a single 300 mg ER tablet per day. Both IV and oral phenytoin will be given for 1 week after traumatic brain injury and then stopped. Comparator= Matching Placebo | Drug | Phenytoin |
| LevetiracetamThe Levetiracetam group will receive 25-30 mg/kg/d in two divided doses (rounded to 750 mg, administered intravenously every 12 hourly). The intravenous dose will be switched to oral form once the patient is fit to take it orally or via Ryles tube. The oral dose would be two tablets of 750 mg ER (extended-release) levetiracetam daily. Both IV and/or oral doses of levetiracetam will be given only for 1 week after head trauma. Patient= Patients with Traumatic brain injury as per eligibility criteria. Intervention= Levetiracetam IV dosing will be 25-30 mg/Kg/d in 2 divided doses (rounded to 750 mg IV BD) followed by 2 tablets of 750 mg ER once patient fit to take orally or via Ryles tube. Comparator= Matching Placebo. | Drug | Levetiracetam |
| PlaceboThe Placebo group will be administered normal saline intravenously of similar amount that of intervention group and matching placebo tablets orally (double dummy) once the patient is fit to take orally. Similar to the intervention group, both IV and oral placebo will be given till 1 week after traumatic brain injury. | Drug | Placebo |
Primary outcome
Number of Participants With Clinical Seizure Within 7 Days Post-Traumatic Brain Injury in each of the three treatment groups.
Time frame: 7 Days
A total of 1260 participants experiencing early clinical seizures (defined as any observable seizure activity occurring within 7 days post-trauma), as recorded by treating clinicians, and confirmed through clinical documentation, during the first 7 days of the study intervention period in each group (Phenytoin, Levetiracetam, Placebo).
4 secondary outcomes
Change in Glasgow Coma Scale scores from baseline at 7 days post-trauma, at 6 months, and 1 year in each treatment group.
Time frame: 7 Days , 6 Months & 1 year
Glasgow Outcome Scale scores at hospital discharge, 6-month, and 1-year follow-up in each treatment group.
Time frame: At discharge, 6 months and 1 year
Incidence of early clinical seizures in participants, assessed in association with CYP2C9 and SV2A gene polymorphisms, using TaqMan allelic discrimination assay with quantitative real-time PCR (qPCR).
Time frame: 7 days
Incremental Cost-Effectiveness Ratio (ICER) of Levetiracetam vs Phenytoin in Preventing Early Post-Traumatic Seizures using Markov chain Monte Carlo simulation.
Time frame: 1 year
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 29 Oct 2026.
- Background: PubMed 28163500Gupta V, Gupta K, Singh G, Kaushal S. An Analytical Study to Correlate Serum Levels of Levetiracetam with Clinical Course in Patients with Epilepsy. J Neurosci Rural Pract. 2016 Dec;7(Suppl 1):S31-S36. doi: 10.4103/0976-3147.196445.
- Background: PubMed 25943175Kousar S, Wafai ZA, Wani MA, Jan TR, Andrabi KI. Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance. Int J Clin Pharmacol Ther. 2015 Jul;53(7):504-16. doi: 10.5414/CP202112.
- Background: PubMed 32510242Chang WC, Hung SI, Carleton BC, Chung WH. An update on CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):723-734. doi: 10.1080/17425255.2020.1780209. Epub 2020 Jul 16.
- Background: PubMed 22551666Dibbens LM, Hodgson BL, Helbig KL, Oliver KL, Mulley JC, Berkovic SF, Scheffer IE. Rare protein sequence variation in SV2A gene does not affect response to levetiracetam. Epilepsy Res. 2012 Sep;101(3):277-9. doi: 10.1016/j.eplepsyres.2012.04.007. Epub 2012 Apr 30.
- Background: PubMed 15866046Schivell AE, Mochida S, Kensel-Hammes P, Custer KL, Bajjalieh SM. SV2A and SV2C contain a unique synaptotagmin-binding site. Mol Cell Neurosci. 2005 May;29(1):56-64. doi: 10.1016/j.mcn.2004.12.011.
- Background: PubMed 18828701Jones KE, Puccio AM, Harshman KJ, Falcione B, Benedict N, Jankowitz BT, Stippler M, Fischer M, Sauber-Schatz EK, Fabio A, Darby JM, Okonkwo DO. Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury. Neurosurg Focus. 2008 Oct;25(4):E3. doi: 10.3171/FOC.2008.25.10.E3.
- Background: PubMed 19898966Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010 Apr;12(2):165-72. doi: 10.1007/s12028-009-9304-y.
- Background: PubMed 30096051Jarvie D, Mahmoud SH. Therapeutic Drug Monitoring of Levetiracetam in Select Populations. J Pharm Pharm Sci. 2018;21(1s):149s-176s. doi: 10.18433/jpps30081.
- Background: PubMed 29177594Cardona AF, Rojas L, Wills B, Bernal L, Ruiz-Patino A, Arrieta O, Hakim EJ, Hakim F, Mejia JA, Useche N, Bermudez S, Carranza H, Vargas C, Otero J, Mayor LC, Ortiz LD, Franco S, Ortiz C, Gil-Gil M, Balana C, Zatarain-Barron ZL. Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma. J Neurooncol. 2018 Jan;136(2):363-371. doi: 10.1007/s11060-017-2660-0. Epub 2017 Nov 25.
- Background: PubMed 1995974Dikmen SS, Temkin NR, Miller B, Machamer J, Winn HR. Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures. JAMA. 1991 Mar 13;265(10):1271-7.
- Background: PubMed 24368357Bhullar IS, Johnson D, Paul JP, Kerwin AJ, Tepas JJ 3rd, Frykberg ER. More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J Trauma Acute Care Surg. 2014 Jan;76(1):54-60; discussion 60-1. doi: 10.1097/TA.0b013e3182aafd15.
- Background: PubMed 6848681Young B, Rapp RP, Norton JA, Haack D, Tibbs PA, Bean JR. Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures. J Neurosurg. 1983 Feb;58(2):236-41. doi: 10.3171/jns.1983.58.2.0236.
- Individual participant dataSharing planned: No
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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.
Dr Jaskaran Singh Gosal Associate Professor, MCh Neurosurgery contact
Dr Shoban Babu Varthya Associate Professor, MD Pharmacology contact
Dr Apinderpreet Singh Additional Professor, MCh Neurosugery principal investigator
Post Graduate Institute of Medical Education and Research, Chandigarh
Dr Kamlesh Bhaisora Additional Professor, MCh Neurosugery principal investigator
Sanjay Gandhi Postgraduate Institute of Medical Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Phenytoin and Levetiracetam in people with Seizures and Traumatic Brain Injuries, run by All India Institute of Medical Sciences, Jodhpur at 3 sites in India.
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 4 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 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Dr Jaskaran Singh Gosal Associate Professor, MCh Neurosurgery (91 6283475891, jhsgosal_87@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinical Seizure Within 7 Days Post-Traumatic Brain Injury in each of the three treatment groups. (time frame: 7 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07072624, which also lists 21 linked publications.
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 29 Oct 2026; AzTrials last refreshed its copy on 31 Oct 2026.