Background and Purpose:During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors of SAE in the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke).Methods:We performed a post hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled clinical trial of magnetic resonance imaging-guided intravenous thrombolysis with alteplase in patients with acute ischemic stroke and unknown time of onset. Functional outcome was assessed by the modified Rankin Scale 90 days after the stroke. SAE were reported to a central safety desk and recorded and categorized by organ system using Medical Dictionary for Regulatory Activities terminology. We used logistic regression analysis to determine the effect of SAE on functional outcome and linear multiple regression analysis to identify baseline predictors of SAE.Results:Among 503 patients randomized, 199 SAE were reported for n=110 (22%) patients. Of those patients who did suffer a SAE, 20 (10%) had a fatal outcome. Patients suffering from at least one SAE had a lower odds of reaching a favorable outcome (modified Rankin Scale score of 0–1) at 90 days (adjusted odds ratio, 0.36 [95% CI, 0.21–0.61], P<0.001). Higher age (P=0.04) and male sex (P=0.01) were predictors for the occurrence of SAE.Conclusions:SAEs were observed in about one in 5 patients, were more frequent in elderly and male patients and were associated with worse functional outcome. These results may help to assess the risk of SAE in future stroke trials and create awareness for severe complications after stroke in clinical practice.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01525290. URL: https://eudract.ema.europa.eu; Unique identifier: 2011-005906-32.

中文翻译：

---

WAKE-UP 试验中急性缺血性卒中的严重不良事件及其对功能结果的影响

背景和目的：在急性缺血性卒中后的最初几天和几周内，患者容易出现并发症，这些并发症会影响进一步的治疗、恢复和功能结果。在临床试验中，严重并发症被记录为严重不良事件 (SAE)。我们在随机对照 WAKE-UP 试验（基于 MRI 的溶栓治疗唤醒卒中的疗效和安全性）中分析了 SAE 对功能结果和 SAE 预测因素的影响。方法：我们对 WAKE-UP 进行了事后分析，一项多中心、随机、安慰剂对照的临床试验，用于磁共振成像引导的阿替普酶静脉溶栓治疗急性缺血性卒中且发病时间未知的患者。中风后 90 天通过改良 Rankin 量表评估功能结果。SAE 被报告给中央安全台，并使用监管活动术语医学词典按器官系统进行记录和分类。我们使用逻辑回归分析来确定 SAE 对功能结果的影响，并使用线性多元回归分析来确定 SAE 的基线预测因子。结果：在随机分配的 503 名患者中，n=110 (22%) 患者报告了 199 例 SAE。在那些确实患有 SAE 的患者中，20 名（10%）有致命的结果。患有至少一种 SAE 的患者在 90 天时达到良好结果（改良 Rankin 量表评分为 0-1）的几率较低（调整后的优势比，0.36 [95% CI，0.21-0.61]，我们使用逻辑回归分析来确定 SAE 对功能结果的影响，并使用线性多元回归分析来确定 SAE 的基线预测因子。结果：在随机分配的 503 名患者中，n=110 (22%) 患者报告了 199 例 SAE。在那些确实患有 SAE 的患者中，20 名（10%）有致命的结果。患有至少一种 SAE 的患者在 90 天时达到良好结果（改良 Rankin 量表评分为 0-1）的几率较低（调整后的优势比，0.36 [95% CI，0.21-0.61]，我们使用逻辑回归分析来确定 SAE 对功能结果的影响，并使用线性多元回归分析来确定 SAE 的基线预测因子。结果：在随机分配的 503 名患者中，n=110 (22%) 患者报告了 199 例 SAE。在那些确实患有 SAE 的患者中，20 名（10%）有致命的结果。患有至少一种 SAE 的患者在 90 天时达到良好结果（改良 Rankin 量表评分为 0-1）的几率较低（调整后的优势比，0.36 [95% CI，0.21-0.61]，P <0.001)。较高的年龄（P = 0.04）和男性（P = 0.01）是 SAE 发生的预测因素。结论：SAE 在大约五分之一的患者中观察到，在老年人和男性患者中更常见，并且与较差的功能结果相关. 这些结果可能有助于评估未来中风试验中 SAE 的风险，并在临床实践中提高对中风后严重并发症的认识。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT01525290。网址：https://eudact.ema.europa.eu；唯一标识符：2011-005906-32。