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. 2025 May 21;25(1):911.
doi: 10.1186/s12885-025-14305-7.

Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial

Archya Dasgupta  1   2 , Shakthivel Mani  3   4 , Abhishek Chatterjee  3   4 , Sadhana Kannan  5   4 , Aliasgar Moiyadi  6   4 , Prakash Shetty  6   4 , Vikas Singh  6   4 , Nandini Menon  7   4 , Arpita Sahu  8   4 , Amitkumar Choudhary  8   4 , Kajari Bhattacharya  8   4 , Ameya Puranik  9   4 , Indraja Dev  9   4 , Sridhar Epari  10   4 , Ayushi Sahay  10   4 , Aekta Shah  10   4 , Nazia Bano  5 , Farnaz Shaikh  5 , Tejpal Gupta  3   4
Affiliations

Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial

Archya Dasgupta et al. BMC Cancer. .

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.

Keywords: Antiepileptics; Brain tumor; Glioma; Levetiracetam; Seizures.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study is being conducted in accordance with ICMR (2017) “National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines, Good Clinical Practice and the principles of the Declaration of Helsinki. The study, including all the study-related documents, has obtained approval from the Ethics Committee prior to the enrolment of participants. The trial has been registered with Clinical Trial Registry of India (CTRI/2024/06/069498) and Clinicaltrials.gov (study identifier NCT06442748). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: All the study investigators declare no conflict of interest in the conduct or outcome of the study.

Figures

Fig. 1
Fig. 1
Workflow of the study
See this image and copyright information in PMC

References

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