IV Fosphenytoin for Acute Trigeminal Neuralgia: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

IV medications for acute TN exacerbations have not been investigated in randomized controlled trials (RCTs).

尚未有随机对照试验（RCTs）研究用于急性TN发作的静脉给药治疗。

Oral medications are often insufficient for acute attacks, and surgery is not immediately available.

口服药物通常不足以治疗急性发作，且手术无法立即进行。

We conducted an RCT to evaluate IV fosphenytoin therapy (IFT) as a rapid-acting rescue treatment for acute TN exacerbations.

我们进行了一项随机对照试验（RCT），以评估静脉注射磷苯妥英钠治疗（IFT）作为急性三叉神经痛（TN）加重的快速救援治疗。

We hypothesized that, compared with placebo, IFT would reduce acute TN pain.

我们假设，与安慰剂相比，IFT会减轻急性TN疼痛。

Methods

This multicenter, double-blind, placebo-controlledphase 3 trial was conducted at 6 institutions (April 2023-April 2024).

这项多中心、双盲、安慰剂对照的III期试验在6个机构进行（2023年4月至2024年4月）。

Patients with classical or idiopathic TN who were experiencing TN exacerbation (numerical rating scale [NRS] score ≥5) were recruited from emergency and outpatient settings, and all study drugs were administered during hospital admission.

招募了经历三叉神经痛加重（数字评分量表[NRS]评分≥5）的经典型或特发性三叉神经痛患者，这些患者来自急诊和门诊，所有研究药物均在住院期间给予。

Participants were randomized 1:1 to IFT (initial dose: 18 mg/kg, maintenance: 7.5 mg/kg for 4 days) or placebo.

参与者按1:1的比例随机分配到IFT（初始剂量：18 mg/kg，维持剂量：7.5 mg/kg，持续4天）或安慰剂。

The primary end point was the change in NRS pain scores from baseline to 120 minutes after the initial dose.

主要终点是基线至首次剂量后120分钟NRS疼痛评分的变化。

Secondary end points included attack frequency, the proportion achieving ≥50% NRS score improvement, and adverse events.

次要终点包括发作频率、达到≥50% NRS评分改善的比例以及不良事件。

Data were collected by blinded personnel and analyzed using repeated-measures mixed-effects models.

数据由不知情的人员收集，并使用重复测量混合效应模型进行分析。

Results

Of 31 participants screened, 22 were randomized; 1 placebo-assigned participant did not meet the NRS ≥5 criterion and was excluded, leaving 21 for analysis (IFT: 11; placebo: 10).

在筛选的31名参与者中，有22人被随机分配；1名被分配安慰剂的参与者未达到NRS≥5的标准，被排除在外，剩余21人用于分析（IFT：11人；安慰剂：10人）。

Participants had a mean age of 65.2 years (range 42-83; 8 men, 13 women).

参与者平均年龄为65.2岁（年龄范围42-83岁；男性8人，女性13人）。

Compared with placebo, IFT significantly reduced pain (NRS change: -6.1 vs -2.4; between-group difference -3.8; 95% CI -6.4 to -1.1; p = 0.008), decreased attack frequency within 24 hours (2.5 ± 5.3 vs 16.1 ± 19.6, difference -13.6; 95% CI -26.4 to -0.7), and increased the proportion achieving ≥50% NRS improvement (90.9% vs 40.0%, difference 50.9%; 95% CI 5.6%-81.6%).

与安慰剂相比，IFT显著减轻了疼痛（NRS变化：-6.1对比-2.4；组间差异-3.8；95%置信区间-6.4至-1.1；p=0.008），24小时内减少了发作频率（2.5±5.3对比16.1±19.6，差异-13.6；95%置信区间-26.4至-0.7），并且增加了达到≥50% NRS改善的比例（90.9%对比40.0%，差异50.9%；95%置信区间5.6%-81.6%）。

Adverse events (somnolence, hypotension, and nausea) were mild and transient.

不良事件（嗜睡、低血压和恶心）是轻微且短暂的。

Discussion

IFT provided rapid and well-tolerated pain relief in acute TN exacerbations.

IFT在急性三叉神经痛发作中提供了快速且耐受性好的疼痛缓解。

Although findings are preliminary because of the small sample size, IFT may be a viable short-term treatment option, meriting further investigation.

尽管由于样本量小，结果尚属初步，但IFT可能是一种可行的短期治疗选择，值得进一步研究。

trial_registration_information

Japan Registry of Clinical Trials, jRCT2011220043.

日本临床试验注册中心，jRCT2011220043。

Registered March 3, 2023.

注册日期为2023年3月3日。

First enrollment April 25, 2023. jrct.mhlw.go.jp/en-latest-detail/jRCT2011220043.

首次招募于2023年4月25日开始。详情请见 jrct.mhlw.go.jp/en-latest-detail/jRCT2011220043。

classification_of_evidence

This study provides Class I evidence that in patients with acute TN exacerbations, IV fosphenytoin is superior to placebo in reducing pain intensity at 120 minutes.

本研究提供了I类证据，表明在急性三叉神经痛急性发作的患者中，静脉注射磷苯妥英比安慰剂更能显著降低120分钟时的疼痛强度。

Results

This study provides Class I evidence that in patients with acute TN exacerbations, IV fosphenytoin is superior to placebo in reducing pain intensity at 120 minutes.

本研究提供了I类证据，表明在急性三叉神经痛急性发作的患者中，静脉注射磷苯妥英比安慰剂更能显著降低120分钟时的疼痛强度。