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

• Published in: BMC cancer Vol. 25; no. 1; pp. 911 - 7
• Main Authors: Dasgupta, Archya, Mani, Shakthivel, Chatterjee, Abhishek, Kannan, Sadhana, Moiyadi, Aliasgar, Shetty, Prakash, Singh, Vikas, Menon, Nandini, Sahu, Arpita, Choudhary, Amitkumar, Bhattacharya, Kajari, Puranik, Ameya, Dev, Indraja, Epari, Sridhar, Sahay, Ayushi, Shah, Aekta, Bano, Nazia, Shaikh, Farnaz, Gupta, Tejpal
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.05.2025; BioMed Central; BMC
• Subjects: Adjuvants; Adult; Analysis; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Antiepileptics; Brain; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - drug therapy; Brain tumor; Brain tumors; Causes of; Clinical trials; Clinical Trials, Phase III as Topic; Complications and side effects; Consent; Convulsions & seizures; Dosage and administration; Drug Administration Schedule; Drug interactions; Drug therapy; Drugs; Edema; Epilepsy; Etiracetam; Female; Glioma; Histology; Humans; Levetiracetam; Levetiracetam - administration & dosage; Levetiracetam - adverse effects; Levetiracetam - therapeutic use; Male; Metastases; Metastasis; Middle Aged; Neurotoxicity; Oncology; Patient outcomes; Patients; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Seizures (Medicine); Seizures - drug therapy; Seizures - etiology; Seizures - prevention & control; Study Protocol; Surgery; Survival; Toxicity; Tumors; India; Mumbai India; Brain tumor; Antiepileptics; Glioma; Levetiracetam; Seizures
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-025-14305-7

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. 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. 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. The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. Registered with CTRI/2024/06/069498, Clinicaltrials.gov: NCT06442748.