Short Versus Long-term Levetiracetam in Brain Tumors (LIBRA)

February 11, 2026 updated by: Dr Archya Dasgupta, Tata Memorial Centre

Short Versus Long-term Levetiracetam in Brain Tumors: A Phase 3 Randomized Controlled Trial (LIBRA)

Levetiracetam is the commonly preferred anti-seizure medicine in patients with brain tumors. This drug has reduced the risk of seizure events occurring but is associated with a risk of side effects such as increased headache, drowsiness, loss of muscle coordination, and psychological challenges in patients. In patients undergoing appropriate treatment for brain tumors and controlled of seizures in the initial few months of levetiracetam, the chance of further seizures is relatively low. The optimal duration to give levetiracetam is not well defined for these patients, and currently as standard treatment levetiracetam is continued for 2-3 years. This study aims to answer this question by comparing patients on a short course of levetiracetam (experimental arm) versus a longer course of levetiracetam (standard arm), with the anticipation that a shorter duration of treatment will not lead to increased seizure episodes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with prior history of seizure from primary brain tumor in the supratentorial location with controlled seizure on levetiracetam monotherapy for at least six months will be considered for the study. Patients more than 18 years of age with KPS ≥ 50 will be eligible. Patients will be randomized in one of the two arms (standard arm or experimental arm) in a 1:1 ratio and stratified based on seizure type, location, histology, tumor grade, and adjuvant therapy. Randomization will be done by the statistician via computerized software using a permuted block design. In the standard arm, patients will continue on the same dose and schedule of levetiracetam (typically prescribed in the range of 1000-3000 mg/ day in 2-3 divided doses) for a duration of 2 years. In the experimental arm, levetiracetam will be tapered by 250- 500 mg every week and stopped. Follow-ups will be done every 3-6 months as per standard practice for the given tumor histology. Neuroimaging will be done 6-12 monthly as per routine clinical practice. The quality-of-life assessment will be done every six months. The primary endpoint is 2-year seizure free survival calculated from the time of randomization.

Patients will continue to receive standard treatment, including adjuvant therapy as standard practice. In case in either arm, the patient develops a seizure episode after stopping levetiracetam will be restarted on levetiracetam monotherapy. If a patient develops a seizure episode while on levetiracetam monotherapy, further add-on antiepileptics will be considered as per standard practice by the responsible physician. Any complications arising from previous treatments (e.g., radio necrosis) or recurrent disease during the study period will be managed according to standard institutional practice without any influence of the study.

An interim analysis is planned for harm or futility to stop the trial when quarter of the expected events have occurred (25% information time), if the observed HR is equal to or greater than the non-inferiority margin (1.47).

At the interim analysis, the one-sided P-value is calculated for testing the hypothesis HR = 1 versus the alternative HR > 1.73 (the experimental treatment is doing worse than the standard treatment). If the P-value is <0.0110 at the interim analysis, the trial would stop with the conclusion that non-inferiority cannot be claimed.

The study will be conducted at Tata Memorial Centre and Manipal Academy of Higher Education with a total sample size of 604 patients for a duration of seven years.

Study Type

Interventional

Enrollment (Estimated)

604

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • India
    • Karnataka
      • Udupi, Karnataka, India, 576104
        • Not yet recruiting
        • Manipal Academy of Higher Education
        • Contact:
        • Principal Investigator:
          • Umesh Velu
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Recruiting
        • Tata Memorial Centre
        • Contact:
        • Principal Investigator:
          • Archya Dasgupta

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria: • Age ≥ 18years

  • History of seizure
  • Histological diagnosis of primary brain tumor
  • Supratentorial location of primary tumor
  • Controlled on levetiracetam monotherapy for 6 months
  • Index surgery within 1 year
  • Karnofsky Performance Scale (KPS) ≥ 50

Exclusion Criteria:

  • KPS < 50
  • No history of seizure
  • Unclear history of seizure episodes in the past
  • Use of antiepileptics other than levetiracetam in the previous 6 months
  • No histological diagnosis
  • Progressive disease
  • Brain metastasis
  • Altered mental status with deficits in understanding or inability to consent to the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: STANDARD
In the standard arm, patients will continue on the same dose and schedule of levetiracetam (prescribed in the range of 1000-3000 mg/ day in 2-3 divided doses) for a duration of 2 years.
Drug: Levetiracetam
Levetiracetam is usually preferred in brain tumor-related epilepsy. Levetiracetam is a second-generation antiepileptic drug that binds to synaptic vesicle glycoprotein SV2A, which interferes with the release of neurotransmitters from the synaptic vesicle and control seizure by multiple mechanisms.
Experimental: EXPERIMENTAL
In the experimental arm, levetiracetam will be tapered by 250- 500 mg every week and then stopped.
Drug: Levetiracetam
Levetiracetam is usually preferred in brain tumor-related epilepsy. Levetiracetam is a second-generation antiepileptic drug that binds to synaptic vesicle glycoprotein SV2A, which interferes with the release of neurotransmitters from the synaptic vesicle and control seizure by multiple mechanisms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year seizure free survival
Time Frame: 7 year
Seizure-free survival measured using Kaplan-Meier product limit method survival calculated from the time of randomization.
7 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 7 year
Overall survival calculated using Kaplan-Meier product-limit method. Death from any cause will be considered as an event.
7 year
Progression-free survival
Time Frame: 7 year
Progression-free survival calculated using Kaplan-Meier product-limit method. Date of radiological progression will be considered as an event.
7 year
Cost-benefit analysis Cost-benefit analysis
Time Frame: 7 year
Cumulative cost of antiepileptic medications and cost of management of seizures between the two groups will be compared using proportions of expenditure.
7 year
Quality of life core questionnaire
Time Frame: 7 year
The European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) core questionnaire (C30) will be used. The summary scores will be calculated from the raw scores as per the manual, ranging from 0 to 100, with higher scores representing better outcomes. The global score and scores of subdomains will be calculated during follow-up and compared with baseline.
7 year
Quality of life brain cancer module
Time Frame: 7 year
The European Organization for Research and Treatment of Cancer (EORTC) brain module (BN20) questionnaire will be used. The summary scores will be calculated from the raw scores as per the manual, ranging from 0 to 100, with higher scores representing better outcomes. The global score and scores of subdomains will be calculated during follow-up and compared with baseline.
7 year
Seizure-free survival between two arms using death as a competing risk
Time Frame: 7 years
Competing risk will be analyzed using Fine and Gray using death as a competing event for seizure.
7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Collaborators

Manipal Academy for Higher Education

Investigators

  • Principal Investigator: Archya Dasgupta, Tata Memorial Centre Mumbai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 4, 2024

Primary Completion (Estimated)

June 1, 2031

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

May 20, 2024

First Submitted That Met QC Criteria

May 29, 2024

First Posted (Actual)

June 4, 2024

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 11, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4385

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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