Levetiracetam for Seizure Prevention After Brain Tumor Surgery

Официальное название

Perioperative Randomized Evaluation of leVetiracetam's Efficacy and Safety for Epilepsy Prevention in Neurosurgical Tumor Patients (PREVENT): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Parallel Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Levetiracetam
  Levetiracetam 500 mg (5 mL) for intravenous infusion administered 1 hour before surgery and again on the evening after surgery (approximately 20:00-22:00), diluted in 100 mL 0.9% sodium chloride or 5% glucose and infused over about 15 minutes. From postoperative day 2 through 3 months, oral levetiracetam tablets 0.5 g twice daily (or via nasogastric route if oral intake not feasible) are administered.
• Препарат Placebo
  Matching placebo solution (5 mL) for intravenous infusion 1 hour before surgery and again on the evening after surgery (approximately 20:00-22:00), diluted in 100 mL 0.9% sodium chloride or 5% glucose and infused over about 15 minutes. From postoperative day 2 through 3 months, matching placebo tablets are given twice daily (oral or via nasogastric route). Placebo formulation, packaging, and administration schedule are identical to those of levetiracetam.

Первичные конечные точки

• Incidence of postoperative clinical seizures within 90 days after surgery [Срок оценки: Within 90 days after surgery]

Вторичные конечные точки (2)

• Incidence of postoperative subclinical seizures detected by EEG [Срок оценки: Within 7 days and 3 months after surgery]
• Safety outcomes: incidence of adverse events, serious adverse events, and all-cause mortality within 3 months after surgery [Срок оценки: Within 3 months after surgery]

Критерии участия

Критерии включения

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

Критерии исключения

• Concomitant brain injury (such as cerebrovascular accident, severe head trauma) or any intracranial disease other than tumor.
• Pregnant or lactating women.
• Intestinal stoma, cardiac disease, previous craniotomy for brain tumor resection, or intracranial infection.
• 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).
• 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).
• Long-term history of psychiatric disorders, alcoholism, or drug abuse.
• Severe mental illness.
• Allergy to or contraindication for antiepileptic drugs.
• Unable to undergo MRI or EEG examination.
• Deemed unsuitable for participation by the investigator.
• Participation in another drug or device clinical trial within the past 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07239115 · KY2025-213-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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