Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial.

Although open-label studies and meta-analyses have suggested that early intravenous thrombolysis might improve visual acuity, no randomised controlled trials have yet confirmed this benefit.

尽管开放标签研究和荟萃分析表明早期静脉溶栓可能改善视力，但尚无随机对照试验确认这一益处。

We aimed to compare the safety and efficacy of intravenous alteplase with oral aspirin in patients with CRAO treated within 4·5 h of onset of severe vision loss.

我们旨在比较静脉注射阿替普酶与口服阿司匹林在治疗起病4.5小时内严重视力丧失的CRAO患者的安全性和有效性。

Methods

THEIA was a multicentre, double-dummy, patient-blinded, assessor-blinded, randomised, controlled, phase 3 trial conducted across 16 hospitals with stroke units in France.

THEIA是一项在法国拥有16家设有卒中单元的医院进行的多中心、双模拟、患者盲法、评估者盲法、随机对照的III期试验。

Adults (aged ≥18 years) presenting with sudden, severe, and persistent monocular vision loss (Snellen <20/400) due to suspected non-arteritic acute CRAO were eligible for inclusion.

年龄≥18岁的成人，如果出现突发的、严重的、持续的单眼视力丧失（Snellen视力表<20/400），且疑似为非动脉炎性急性视网膜中央动脉阻塞（CRAO），则符合纳入标准。

Participants were randomly assigned (1:1), stratified by centre, to receive either 0·9 mg/kg of bodyweight intravenous alteplase and oral placebo (alteplase group) or 300 mg oral aspirin and intravenous saline placebo (aspirin group) within 4·5 h of symptom onset.

参与者按1:1的比例随机分配，按中心分层，于症状发作后4.5小时内接受0.9 mg/kg体重的静脉注射阿替普酶和口服安慰剂（阿替普酶组）或300 mg口服阿司匹林和静脉注射生理盐水安慰剂（阿司匹林组）。

Patients, outcome assessors, and the study sponsor were masked to treatment allocation; treating nurses and neurologists were unmasked.

患者、结果评估者和研究赞助者对治疗分配进行了盲法处理；治疗护士和神经科医生未进行盲法处理。

The primary efficacy outcome was improvement in visual acuity of at least 0·3 logarithm of the minimum angle of resolution (LogMAR) from baseline to 1 month, analysed in the full analysis set, which included all patients who received the complete intervention and a visual acuity assessment at baseline.

主要疗效结果是至少0.3对数最小角度分辨率（LogMAR）的视力改善，从基线到1个月，分析在全分析集（FAS）中进行，该集包括所有接受完整干预并进行了基线视力评估的患者。

Safety outcomes included serious adverse events, particularly intracranial and extracranial bleeding, analysed in all randomly assigned participants.

安全性结果包括严重不良事件，特别是颅内和颅外出血，在所有随机分配的参与者中进行了分析。

This study is registered at ClinicalTrials.gov (NCT03197194) and is completed.

该研究已在ClinicalTrials.gov注册（NCT03197194），研究已完成。

Results

Between June 8, 2018, and Oct 2, 2023, 70 patients (mean age 70 years [SD 9]; 25 [36%] women and 45 [64%] men) were enrolled and randomly assigned to either the alteplase group (35 [50%]) or the aspirin group (35 [50%]).

2018年6月8日至2023年10月2日期间，共有70名患者（平均年龄70岁[标准差9]；25名[36%]女性和45名[64%]男性）被纳入研究并随机分配到阿替普酶组（35名[50%]）或阿司匹林组（35名[50%]）。

In total, 65 (93%) patients received the allocated treatment: 34 (97%) in the alteplase group and 31 (89%) in the aspirin group.

总共65名（93%）患者接受了分配的治疗：阿替普酶组34名（97%），阿司匹林组31名（89%）。

Mean time from symptom onset to treatment initiation was 232·4 min (SD 43·6).

症状发作到治疗开始的平均时间是232.4分钟（标准差43.6分钟）。

Among 56 patients with available data on the primary endpoint, 19 (66%) of 29 patients in the alteplase group and 13 (48%) of 27 patients in the aspirin group showed an improvement in visual acuity of at least 0·3 LogMAR at 1 month (unadjusted risk difference 17·4 [95% CI -11·8 to 46·5]; adjusted odds ratio 1·1 [95% CI 0·07 to 18·39]; p=0·95).

在有主要终点数据的56名患者中，29名接受阿替普酶治疗的患者中有19名（66%），以及27名接受阿司匹林治疗的患者中有13名（48%）在1个月时视力至少提高了0.3 LogMAR（未调整风险差异17.4 [95% 置信区间-11.8至46.5]；调整后的优势比1.1 [95% 置信区间0.07至18.39]；p=0.95）。

One asymptomatic intracranial haemorrhage related to study treatment was reported in the alteplase group. 14 serious adverse events unrelated to treatment occurred in 11 patients overall (six [17%] in the aspirin group and five [14%] in the alteplase group).

在使用阿替普酶组中报告了一例与研究治疗相关的无症状颅内出血。在总共11名患者中发生了14起与治疗无关的严重不良事件（阿司匹林组六例[17%]，阿替普酶组五例[14%]）。

No symptomatic haemorrhages or major bleeding related to study treatment were reported.

未报告与研究治疗相关的症状性出血或主要出血事件。

interpretation

Intravenous alteplase administered within 4·5 h of CRAO onset was not associated with a significant improvement in visual acuity compared with aspirin, despite a higher rate of improvement in the alteplase group.

在中央性视网膜动脉阻塞（CRAO）发作后4.5小时内静脉注射阿替普酶与阿司匹林相比，并没有显著改善视力，尽管阿替普酶组的改善率更高。

However, the study was likely underpowered to detect a statistical difference.

然而，该研究可能缺乏足够的统计功效来检测统计差异。

Although no safety concerns related to alteplase were identified, the overall modest recovery rates underscore the need for individual patient-level data meta-analyses with forthcoming randomised controlled trials to clarify the potential benefit of thrombolysis or aspirin in patients with acute CRAO.

尽管未发现与阿替普酶相关的安全问题，但总体上适度的恢复率强调了需要对即将到来的随机对照试验进行个体患者水平数据的荟萃分析，以阐明急性视网膜中央动脉阻塞患者接受溶栓或阿司匹林治疗的潜在益处。

funding

French Ministry of Health and Boehringer Ingelheim, France.

法国卫生部和法国勃林格殷格翰公司。