Can Perampanel Prevent Seizures After Craniotomy for Brain Tumors?

December 24, 2024

Craniotomy, a common surgical procedure performed to remove brain tumors, carries a significant risk of inducing seizures in patients, a complication that can lead to increased cerebral pressure, aspiration pneumonia, and prolonged hospital stays. Although guidelines generally discourage routine use of antiseizure drugs owing to insufficient efficacy data, many practitioners still prescribe them. This discrepancy highlights the necessity for robust evidence, which the GRAMPAS trial aims to provide.

Background and Rationale

Seizures following craniotomy are notable perioperative complications that often lead to severe adverse outcomes. Despite clinical guidelines advising against the routine use of antiseizure medications due to a lack of supporting data, physicians frequently prescribe these medications. This inconsistency points toward a pressing need for conclusive evidence regarding the preventive effectiveness of antiseizure drugs during the perioperative period. The GRAMPAS trial seeks to address this gap and reconcile current clinical practices with established guidelines.

Study Design and Methods

To evaluate the preventive effects of perampanel on epileptogenesis induced by craniotomy, the GRAMPAS trial will be conducted at five hospitals in Nagoya, Japan, from February 2024 to December 2026. The trial will involve 142 patients who have never experienced seizures and have supratentorial brain tumors. Participants will be randomly divided into two groups: one receiving 2 mg of perampanel and the other receiving no antiseizure medication.

Starting two days before surgery, the treatment group will continue taking perampanel until 28 days post-operation. In contrast, the control group will receive no prophylactic antiseizure drugs, adhering to current guidelines. The primary outcome measured will be the incidence of seizures within 28 days of craniotomy. Secondary outcomes will focus on hospital and ICU stay lengths, along with other postoperative complications.

Objectives and Hypotheses

The primary objective of the GRAMPAS trial is to assess whether perampanel can effectively reduce early postoperative seizures compared to no treatment. Researchers hypothesize that due to its rapid and high transfer from blood to the central nervous system and its long half-life, perampanel will prevent early postoperative seizures more efficiently than no treatment.

Patient Selection Criteria

For inclusion in the GRAMPAS trial, patients must be aged between 18 and 80, have a Karnofsky Performance Scale score above 70, and exhibit supratentorial brain tumors. Exclusion criteria include the inability to take tablets orally, being indicated for awake surgery, having other central nervous system diseases, or having used antiseizure medication other than perampanel within a week leading up to surgery. This careful selection ensures the study’s integrity and the safety of participants.

Data Collection and Analysis

The GRAMPAS trial will gather comprehensive data encompassing demographic information, medical history, clinical characteristics, imaging findings, and pathological reports. Researchers will meticulously monitor adverse events and adherence to the treatment regimen. Data management will utilize an electronic data capture system, and statistical analysis will involve Fisher’s exact test for primary endpoints and the Mann-Whitney U test for secondary outcomes.

Safety and Monitoring

The trial incorporates strict safety assessments and monitoring protocols to ensure participant safety and data accuracy. Adverse events will be documented as per standardized criteria, and perampanel will be discontinued in cases of grade 3 or higher adverse events. A dedicated monitoring committee will oversee the trial, ensuring compliance with safety regulations and maintaining the study’s ethical standards.

Ethical Considerations

The ethics committee of Nagoya University Hospital has granted ethical approval for the study, which is registered with the Japan Registry of Clinical Trials. All participating patients will provide written informed consent, ensuring they fully understand the study and their involvement. Ethical considerations are paramount to the trial’s execution, ensuring transparency and participant welfare throughout the study.

Potential Impact and Future Directions

As the first multi-center, randomized trial focused on investigating the use of low-dose perampanel for preventing postoperative seizures, the GRAMPAS trial has the potential to significantly alter clinical guidelines and perioperative practices. If proven effective, perampanel might become the standard practice, replacing the current heterogeneous use of antiseizure drugs that often lack prospective validation. This could lead to more standardized and effective perioperative care, ultimately improving patient outcomes.

Conclusion

Craniotomy, a frequently performed surgical procedure to remove brain tumors, comes with a substantial risk of causing seizures in patients. This serious complication can lead to an array of issues, including increased cerebral pressure, aspiration pneumonia, and longer hospital stays. Despite guidelines generally advising against the routine use of antiseizure medications due to a lack of strong efficacy data, many medical professionals continue to prescribe these drugs to mitigate the risk of post-surgery seizures. This ongoing practice reveals a gap in definitive evidence regarding the effectiveness and necessity of these medications. To address this critical issue, the GRAMPAS trial has been initiated. This trial aims to provide robust and conclusive evidence on whether the routine use of antiseizure drugs in craniotomy patients is beneficial. The findings from this trial could potentially influence future guidelines and standard practices, ensuring better patient outcomes while minimizing unnecessary medication use.

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