Background Remote ischemic conditioning (RIC) can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage (ICH).

Aims This study aimed to evaluate the safety and preliminary efficacy of RIC in patients with ICH.

Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial ICH presenting within 24-48 hours of onset were randomly assigned to receive medical therapy plus RIC for consecutive 7 days or medical therapy alone. The primary safety outcome was neurological deterioration within 7 days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 d ([hematoma volume at 7 d − hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days.

Results The mean age was 59.3±11.7 years and hematoma volume was 13.9±4.5 mL. No subjects experienced neurological deterioration within 7 days of enrollment, and no subject died or experienced RIC-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19±5.07 mL in the control group and 13.55±3.99 mL in the RIC group, and they were 8.54±3.99 mL and 6.95±2.71 mL at 7 days after enrollment, respectively, not a significant difference (p>0.05 each). The hematoma resolution rate in the RIC group (49.25±9.17%) was significantly higher than in the control group (41.92±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015). The absolute PHE volume was 17.27±8.34 mL in the control group and 12.92±7.30 mL in the RIC group at 7 days after enrollment, not a significant between-group difference (p=0.087), but the relative PHE in the RIC group (1.77±0.39) was significantly lower than in the control group (2.02±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023). At 90-day follow-up, 13 subjects (65%) in the RIC group and 12 subjects (60%) in the control group achieved favorable functional outcomes (mRS score≤3), not a significant between-group difference (p=0.744).

Conclusions Repeated daily RIC for consecutive 7 days was safe and well-tolerated in patients with ICH, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, effects RIC on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations.

Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.

背景远程缺血调理 (RIC) 可以促进脑出血 (ICH) 动物模型中的血肿消退、减轻脑水肿和改善神经功能恢复。

目的 本研究旨在评估 RIC 在 ICH 患者中的安全性和初步疗效。

方法 在这项多中心、随机、对照试验中，40 名在发病 24-48 小时内出现的幕上 ICH 受试者被随机分配接受药物治疗加 RIC 连续 7 天或单独药物治疗。主要安全性结果是入组后 7 天内的神经功能恶化，主要疗效结果是 CT 图像上血肿体积的变化。其他结果包括 7 天时的血肿消退率（[7 天时的血肿体积 - 基线时的血肿体积]/基线时的血肿体积）、血肿周围水肿 (PHE) 和 90 天时的功能结果。

结果平均年龄为 59.3±11.7 岁，血肿体积为 13.9±4.5 毫升。入组后 7 天内没有受试者出现神经功能恶化，在研究期间没有受试者死亡或经历 RIC 相关的不良事件。基线时，对照组血肿体积为 14.19±5.07 mL，RIC 组为 13.55±3.99 mL，入组后 7 天分别为 8.54±3.99 mL 和 6.95±2.71 mL，而不是显着差异（每个 p>0.05）。RIC 组的血肿消退率 (49.25±9.17%) 明显高于对照组 (41.92±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015)。入组后 7 天，对照组的绝对 PHE 体积为 17.27±8.34 mL，RIC 组为 12.92±7.30 mL，组间差异不显着（p=0.087），但 RIC 组的相对 PHE (1.77±0.39) 显着低于对照组 (2.02±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023)。在 90 天的随访中，RIC 组的 13 名受试者 (65%) 和对照组的 12 名受试者 (60%) 取得了良好的功能结果 (mRS 评分≤3)，组间差异不显着 (p =0.744）。

结论 连续 7 d 每日重复 RIC 对 ICH 患者安全、耐受性好，可提高血肿消退率，降低相对 PHE。然而，RIC 对该患者群体的绝对血肿和 PHE 体积和功能结果的影响需要进一步研究。

临床试验注册网址：http://www.clinicaltrials.gov。唯一标识符：NCT03930940。