A multi-center, open-label, randomized clinical trial is being conducted across five hospitals in Nagoya, Japan, to assess the preventive effect of perampanel (PER) on early seizures following craniotomy for brain tumors. The study, registered in the Japan Registry of Clinical Trials (jRCTs041230117), aims to determine if prophylactic administration of PER can reduce the incidence of postoperative seizures, a common and potentially debilitating complication. The trial is scheduled from February 2024 to December 2026.
Study Design and Patient Selection
The trial will enroll patients aged 18 to 80 years with supratentorial brain tumors scheduled for craniotomy. Eligible patients include those with intra-axial tumors, extra-axial tumors with brain edema, or extra-axial tumors without brain edema compressing the motor cortex, deemed at high risk for early seizures by their physicians. Key inclusion criteria also involve a Karnofsky Performance Scale score above 70 and no documented history of seizures. Exclusion criteria encompass patients unable to take oral medication, those indicated for awake surgery, or individuals with other central nervous system diseases.
Treatment Protocol and Randomization
Participants will be randomized (1:1) to either the treatment group, receiving 2 mg of PER daily for two days before and 28 days after surgery, or the control group, receiving standard care without prophylactic antiseizure medication. Randomization will be stratified by tumor type, sex, age, and institution using a minimization method. Postoperative blood PER levels will be measured in the treatment group to monitor drug exposure. In the event of a seizure in either group, antiseizure medication will be administered at the discretion of the treating physician.
Outcomes and Data Analysis
The primary outcome is the incidence of seizures within 28 days postoperatively. Secondary outcomes include the length of hospital stay, ICU stay, and incidence of postoperative complications. Data will be collected using an electronic data capture system (REDCap) and analyzed by a data management team blinded to the treatment allocation. Statistical analysis will primarily use Fisher’s exact test to compare seizure incidence between groups, with a one-sided significance level of 0.05 to test the superiority of PER over the control group.
Safety and Monitoring
Adverse events (AEs) will be monitored and recorded according to the Common Terminology Criteria for Adverse Events version 5.0. Comparative analyses of AE incidence between the treatment and control groups will be conducted using Fisher’s exact test for each AE category. AEs will also be assessed for their relationship to the treatment. A monitoring committee will oversee patient safety and data collection, with regular on-site and off-site monitoring. Any grade 3 or higher AEs attributed to the treatment will be immediately reported to the monitoring committee for evaluation.
Significance
This trial addresses a critical need for effective strategies to prevent postoperative seizures in patients undergoing craniotomy for brain tumors. The results will provide valuable insights into the efficacy and safety of perampanel as a prophylactic agent in this setting, potentially influencing clinical practice and improving patient outcomes.
