Assessing Phenytoin and Levetiracetam Efficacy, Cost-Effectiveness, and CYP2C9/SV2A Polymorphism in Early Post-Traumatic Seizures: A Multicentric Prospective Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,260
- 试验地点
- 3
- 主要终点
- Number of Participants With Clinical Seizure Within 7 Days Post-Traumatic Brain Injury in each of the three treatment groups.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of severe blunt TBI with GCS score less than
- •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.
排除标准
- •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.
研究组 & 干预措施
Phenytoin
干预措施: Phenytoin (Drug)
Levetiracetam
干预措施: Levetiracetam (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Clinical Seizure Within 7 Days Post-Traumatic Brain Injury in each of the three treatment groups.
时间窗: 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).
次要结局
- Change in Glasgow Coma Scale scores from baseline at 7 days post-trauma, at 6 months, and 1 year in each treatment group.(7 Days , 6 Months & 1 year)
- Glasgow Outcome Scale scores at hospital discharge, 6-month, and 1-year follow-up in each treatment group.(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).(7 days)
- Incremental Cost-Effectiveness Ratio (ICER) of Levetiracetam vs Phenytoin in Preventing Early Post-Traumatic Seizures using Markov chain Monte Carlo simulation.(1 year)
研究者
Jaskaran Singh Gosal
Associate Professor
All India Institute of Medical Sciences, Jodhpur