Levetiracetam for Seizure Prevention After Brain Tumor Surgery (PREVENT)

Capital Medical University

Status and phase: Not yet enrolling; Phase 3

Conditions: Postoperative Seizures After Brain Tumor Surgery

Treatments: Drug: Placebo; Drug: Levetiracetam

Study type: Interventional

Funder types: Other

Identifiers

NCT07239115

KY2025-213-02

Details and patient eligibility

About

This study aims to evaluate the efficacy and safety of levetiracetam for the prevention of postoperative seizures in adult patients undergoing supratentorial brain tumor surgery. It is a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. Eligible participants will be randomly assigned in a 1:1 ratio to receive levetiracetam or placebo, starting 1 hour before surgery and continuing for 3 months postoperatively. The primary outcome is the incidence of clinical seizures within 3 months after surgery. Secondary outcomes include subclinical seizures within 7 days and 3 months postoperatively, adverse events within 3 months, and health economic outcomes. The study aims to clarify the role of levetiracetam in the primary prevention of perioperative seizures in brain tumor patients and to provide evidence for rational use of antiseizure medications in neurosurgical practice.

Full description

Seizures are a common complication in brain tumor patients, particularly after supratentorial craniotomy, with approximately two-thirds occurring within the first postoperative month and affecting both early recovery and long-term outcomes. Although prophylactic ASMs are widely used in practice, there is no consensus on whether routine prophylaxis is necessary or on the optimal regimen. Major societies generally conclude that evidence is insufficient to recommend for or against routine use, while some national guidance provides conditional suggestions only for "high-risk" patients-highlighting the lack of robust data. Real-world studies also show high but heterogeneous use and no unified standard. A high-quality randomized trial is therefore required to determine the necessity, efficacy, and safety of routine prophylaxis.

The PREVENT trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of levetiracetam in adults undergoing supratentorial tumor resection without a prior seizure history, and thereby to assess the need for routine perioperative prophylaxis. Participants are randomized 1:1 with center-stratified block allocation. The dosing regimen is: one intravenous dose 1 hour preoperatively and another on the evening after surgery, followed by oral/NG maintenance (0.5 g twice daily) through postoperative month 3; the control arm receives matching placebo. Standard antiseizure treatment is provided if seizures occur and these events are recorded as endpoints. Scheduled assessments occur at screening, day of surgery, postoperative day 7, month 3 (±7 days), and month 6 (±10 days).

The primary endpoint is clinical seizures within 3 months after surgery, adjudicated by predefined criteria. Secondary endpoints are subclinical seizures within 7 days and 3 months (based on standardized EEG review). Exploratory endpoints include direct medical costs and direct non-medical/indirect costs at 3 months, and clinical seizures within 6 months. Safety endpoints include adverse events, serious adverse events, and death through 3 months. The principal null hypothesis is no difference between groups. Efficacy is analyzed primarily in the full analysis set (FAS) with per-protocol (PPS) as supportive; center effects are modeled, two-sided α=0.05, and results reported as risk differences with 95% CIs and relative risks. The planned sample size is 558 participants across ~10 centers, with independent safety oversight. This trial will provide robust randomized evidence on the necessity, benefits, risks, and economic impact of routine perioperative prophylaxis to guide standardized clinical practice.

Enrollment: 558 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Undergoing craniotomy for supratentorial brain tumor resection.
2. Radiologically confirmed supratentorial brain tumor (excluding posterior fossa tumor, brainstem tumor, or gliomatosis cerebri).
3. Age between 18 and 75 years.
4. No history of seizures or epilepsy.
5. No prior use of antiepileptic drugs.
6. Karnofsky Performance Status (KPS) score ≥ 70.
7. Signed written informed consent

Exclusion criteria

1. Concomitant brain injury (such as cerebrovascular accident, severe head trauma) or any intracranial disease other than tumor.
2. Pregnant or lactating women.
3. Intestinal stoma, cardiac disease, previous craniotomy for brain tumor resection, or intracranial infection.
4. Severe hepatic or renal dysfunction (defined as ALT or AST >3× upper limit of normal; serum creatinine >3.0 mg/dL [265.2 μmol/L] or eGFR <30 mL/min/1.73m²).
5. Significant electrolyte imbalance (severe hyponatremia: serum sodium <125 mmol/L; severe hypernatremia: serum sodium >160 mmol/L; severe hypocalcemia: serum calcium <2.5 mmol/L; or severe hypercalcemia: serum calcium >6.5 mmol/L).
6. Long-term history of psychiatric disorders, alcoholism, or drug abuse.
7. Severe mental illness.
8. Allergy to or contraindication for antiepileptic drugs.
9. Unable to undergo MRI or EEG examination.
10. Deemed unsuitable for participation by the investigator.
11. Participation in another drug or device clinical trial within the past 3 months.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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558 participants in 2 patient groups, including a placebo group

Levetiracetam group

Experimental group

Description:

Participants receive levetiracetam 500 mg intravenously 1 hour before surgery and again on the evening after surgery (around 20:00-22:00), followed by oral levetiracetam 0.5 g twice daily from postoperative day 2 through 3 months. Intravenous infusion is given over approximately 15 minutes after dilution in 100 mL 0.9% sodium chloride or 5% glucose.

Treatment:

Drug: Levetiracetam

Placebo group

Placebo Comparator group

Description:

Participants receive matching placebo solution intravenously 1 hour before surgery and again on the evening after surgery (around 20:00-22:00), followed by oral placebo tablets twice daily from postoperative day 2 through 3 months. The placebo is identical in appearance, packaging, and administration schedule to levetiracetam.

Treatment:

Drug: Placebo