Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial
Abstract Background Seizures are common in patients with brain tumors, impacting daily life and healthcare burden. In contemporary neuro-oncology practice, levetiracetam is the most commonly prescribed anti-seizure medication (ASM). Although the practice is widely variable, levetiracetam is usually...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14305-7 |
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| author | Archya Dasgupta Shakthivel Mani Abhishek Chatterjee Sadhana Kannan Aliasgar Moiyadi Prakash Shetty Vikas Singh Nandini Menon Arpita Sahu Amitkumar Choudhary Kajari Bhattacharya Ameya Puranik Indraja Dev Sridhar Epari Ayushi Sahay Aekta Shah Nazia Bano Farnaz Shaikh Tejpal Gupta |
| author_facet | Archya Dasgupta Shakthivel Mani Abhishek Chatterjee Sadhana Kannan Aliasgar Moiyadi Prakash Shetty Vikas Singh Nandini Menon Arpita Sahu Amitkumar Choudhary Kajari Bhattacharya Ameya Puranik Indraja Dev Sridhar Epari Ayushi Sahay Aekta Shah Nazia Bano Farnaz Shaikh Tejpal Gupta |
| author_sort | Archya Dasgupta |
| collection | DOAJ |
| description | Abstract Background Seizures are common in patients with brain tumors, impacting daily life and healthcare burden. In contemporary neuro-oncology practice, levetiracetam is the most commonly prescribed anti-seizure medication (ASM). Although the practice is widely variable, levetiracetam is usually used for 2–3 years following surgery to prevent further seizures. However, the incidence of seizures post antitumoral treatment is relatively low, and the duration of use is not well defined. To address this knowledge gap, the current randomized controlled non-inferiority trial will be conducted comparing a shorter regimen of levetiracetam with the standard long-term schedule. Methods and analysis Patients with newly diagnosed primary brain tumors (brain metastasis excluded) in the supratentorial compartment with a prior history of seizure will be eligible for the study. Adults (> 18 years), within 1 year from surgery, and controlled on levetiracetam monotherapy for 6 months will be randomized in a 1:1 ratio to either standard arm (long course: additional 2 years levetiracetam) or experimental arm (short course: tapered of levetiracetam and stopped). Stratification factors include tumor location, seizure type, histology, grade, and adjuvant therapy. The primary endpoint is 2-year seizure-free survival (SFS); secondary endpoints include seizure impact, quality of life, progression-free survival (PFS), and overall survival (OS). Assuming a 2-year SFS rate of 80%, a total of 431 patients (167 events) will be needed to prove the non-inferiority of the experimental arm (non-inferiority margin of 8%, α = 0.05, power = 80%). Considering an attrition rate of 40% (25% accounting for death and 15% lost to follow-up), the final sample size is 604. Discussion The trial will provide level 1 evidence on the optimal duration of ASM use in primary brain tumors with a history of seizures. If short-term ASM use is non-inferior, it will reduce drug utilization, lower neurotoxicity, improve quality of life, and optimize resource usage. Ethics and dissemination The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. Registration Registered with CTRI/2024/06/069498, Clinicaltrials.gov: NCT06442748. |
| format | Article |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-eebf564cd2324569aaceb305c8395ba12025-08-20T01:53:19ZengBMCBMC Cancer1471-24072025-05-012511710.1186/s12885-025-14305-7Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trialArchya Dasgupta0Shakthivel Mani1Abhishek Chatterjee2Sadhana Kannan3Aliasgar Moiyadi4Prakash Shetty5Vikas Singh6Nandini Menon7Arpita Sahu8Amitkumar Choudhary9Kajari Bhattacharya10Ameya Puranik11Indraja Dev12Sridhar Epari13Ayushi Sahay14Aekta Shah15Nazia Bano16Farnaz Shaikh17Tejpal Gupta18Department of Radiation Oncology, Tata Memorial CentreDepartment of Radiation Oncology, Tata Memorial CentreDepartment of Radiation Oncology, Tata Memorial CentreClinical Research Secretariat, Tata Memorial CentreNeurosurgical Oncology Services, Department of Surgical Oncology, Tata Memorial CentreNeurosurgical Oncology Services, Department of Surgical Oncology, Tata Memorial CentreNeurosurgical Oncology Services, Department of Surgical Oncology, Tata Memorial CentreDepartment of Medical Oncology, Tata Memorial CentreDepartment of Radio-diagnosis, Tata Memorial CentreDepartment of Radio-diagnosis, Tata Memorial CentreDepartment of Radio-diagnosis, Tata Memorial CentreDepartment of Nuclear Medicine, Tata Memorial CentreDepartment of Nuclear Medicine, Tata Memorial CentreDepartment of Pathology, Tata Memorial CentreDepartment of Pathology, Tata Memorial CentreDepartment of Pathology, Tata Memorial CentreClinical Research Secretariat, Tata Memorial CentreClinical Research Secretariat, Tata Memorial CentreDepartment of Radiation Oncology, Tata Memorial CentreAbstract Background Seizures are common in patients with brain tumors, impacting daily life and healthcare burden. In contemporary neuro-oncology practice, levetiracetam is the most commonly prescribed anti-seizure medication (ASM). Although the practice is widely variable, levetiracetam is usually used for 2–3 years following surgery to prevent further seizures. However, the incidence of seizures post antitumoral treatment is relatively low, and the duration of use is not well defined. To address this knowledge gap, the current randomized controlled non-inferiority trial will be conducted comparing a shorter regimen of levetiracetam with the standard long-term schedule. Methods and analysis Patients with newly diagnosed primary brain tumors (brain metastasis excluded) in the supratentorial compartment with a prior history of seizure will be eligible for the study. Adults (> 18 years), within 1 year from surgery, and controlled on levetiracetam monotherapy for 6 months will be randomized in a 1:1 ratio to either standard arm (long course: additional 2 years levetiracetam) or experimental arm (short course: tapered of levetiracetam and stopped). Stratification factors include tumor location, seizure type, histology, grade, and adjuvant therapy. The primary endpoint is 2-year seizure-free survival (SFS); secondary endpoints include seizure impact, quality of life, progression-free survival (PFS), and overall survival (OS). Assuming a 2-year SFS rate of 80%, a total of 431 patients (167 events) will be needed to prove the non-inferiority of the experimental arm (non-inferiority margin of 8%, α = 0.05, power = 80%). Considering an attrition rate of 40% (25% accounting for death and 15% lost to follow-up), the final sample size is 604. Discussion The trial will provide level 1 evidence on the optimal duration of ASM use in primary brain tumors with a history of seizures. If short-term ASM use is non-inferior, it will reduce drug utilization, lower neurotoxicity, improve quality of life, and optimize resource usage. Ethics and dissemination The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. Registration Registered with CTRI/2024/06/069498, Clinicaltrials.gov: NCT06442748.https://doi.org/10.1186/s12885-025-14305-7SeizuresLevetiracetamBrain tumorAntiepilepticsGlioma |
| spellingShingle | Archya Dasgupta Shakthivel Mani Abhishek Chatterjee Sadhana Kannan Aliasgar Moiyadi Prakash Shetty Vikas Singh Nandini Menon Arpita Sahu Amitkumar Choudhary Kajari Bhattacharya Ameya Puranik Indraja Dev Sridhar Epari Ayushi Sahay Aekta Shah Nazia Bano Farnaz Shaikh Tejpal Gupta Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial BMC Cancer Seizures Levetiracetam Brain tumor Antiepileptics Glioma |
| title | Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial |
| title_full | Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial |
| title_fullStr | Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial |
| title_full_unstemmed | Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial |
| title_short | Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial |
| title_sort | study protocol of short versus long term levetiracetam in brain tumors libra a phase 3 randomized controlled trial |
| topic | Seizures Levetiracetam Brain tumor Antiepileptics Glioma |
| url | https://doi.org/10.1186/s12885-025-14305-7 |
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