Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cell Administration (REALIST-COVID) Phase 2 Randomised Controlled Trial
Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cell Administration (REALIST-COVID) Phase 2 Randomised Controlled Trial
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通过基质细胞管理修复 COVID-19 中的急性呼吸窘迫综合征 (REALIST-COVID) 第 2 期随机对照试验
DOI：
10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5285
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Gorman E
中科院分区：
文献类型：
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作者：
Gorman E
间充质间质细胞（MSCs）具有免疫调节和修复作用，可能对急性呼吸窘迫综合征（ARDS）有益。现实主义1期研究证明了ORBCEL-C间充质干细胞在ARDS患者中的安全性。1 . reality COVID 2期研究调查了ORBCEL-C MSCs在COVID-19所致ARDS患者中的安全性和有效性。方法本研究是一项多中心、随机、双盲、分配隐蔽、安慰剂对照的临床试验，纳入了由COVID-19引起的中重度ARDS机械通气患者。参与者被随机分配（1:1）接受ORBCEL-C（富含CD362的脐带来源的MSCs， 400x106细胞）或安慰剂（血浆lyte -148）。主要安全性指标是严重不良事件（SAEs）的发生率。主要疗效指标为第7天的氧合指数（OI）。次要替代结果包括第4天和第7天的OI、呼吸顺应性、驱动压、第4、7和14天的PaO2/FiO2比率和SOFA评分。报告临床结果（包括通气时间和死亡率）。患者随访1年，观察死亡率和重大医疗事件。试验注册NCT03042143。结果从2020年4月2日至12月4日招募了60名参与者（最终分析包括n= 30名ORBCEL-C组和n= 29名安慰剂组，安慰剂组有n= 1名撤回同意）。各组在基线时平衡。ORBCEL-C组发生6例SAEs，安慰剂组发生3例，风险比（RR）为2.9（95%可信区间（CI） 0.6 ~ 13.2, p= 0.25）。第7天，ORBCEL-C组（平均（SD） 98.3(57.2)）和安慰剂组(平均（SD） 96.6(67.3)：平均差异1.8 （95% CI 30.7-34.4, p= 0.91）。两组间替代次要结局无差异（图1）。临床结果不足，但死亡率没有差异(28天死亡率ORBCEL-C为16.7%(n= 5)，安慰剂为20.7%(n= 6)；RR 0.8 (95% CI 0.3-2.4), p= 0.69)，与安慰剂组相比，ORBCEL-C组通气持续时间增加(ORBCEL-C 19天（IQR 13-30），安慰剂12天（IQR 7-20）；风险比0.5 (95% CI 0.3-0.9), p= 0.017)。结论：该2期临床试验支持ORBCEL-C治疗COVID-19所致中至重度ARDS患者的安全性，但未显示出疗效，也不支持在该人群中常规给予ORBCEL-C MSCs。资助威康信托健康创新挑战基金（编号106939/Z/15/Z）和北爱尔兰健康和社会保健研究与发展基金。Gorman等。基质细胞给药修复急性呼吸窘迫综合征（写实）试验：一期试验。EClinicalMedicine 2021;41: 101167。
RATIONALEMesenchymal stromal cells (MSCs) have immunomodulatory and reparative effects which may be of benefit in acute respiratory distress syndrome (ARDS). The REALIST phase 1 study demonstrated safety of ORBCEL-C MSCs in patients with ARDS. 1 The REALIST COVID phase 2 study investigated the safety and efficacy of ORBCEL-C MSCs in patients with ARDS due to COVID-19.METHODSThis was a multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial in mechanically ventilated patients with moderate to severe ARDS, due to COVID-19. Participants were randomised (1: 1) to receive either ORBCEL-C (CD362 enriched umbilical cord-derived MSCs, 400x106 cells) or placebo (Plasma-Lyte-148). The primary safety outcome was the incidence of serious adverse events (SAEs). The primary efficacy outcome was oxygenation index (OI) at day 7. Secondary surrogate outcomes included OI at day 4 and day 7, respiratory compliance, driving pressure, PaO2/FiO2 ratio and SOFA score on days 4, 7, and 14. Clinical outcomes (including duration of ventilation and mortality) are reported. Patients were followed up at 1 year for mortality and significant medical events. Trial registration NCT03042143.RESULTS60 participants were recruited from 2nd April until 4th December 2020 (the final analysis included n= 30 in ORBCEL-C and n= 29 in placebo groups as n= 1 in placebo group withdrew consent). Groups were balanced at baseline. There were 6 SAEs in the ORBCEL-C and 3 in the placebo group, risk ratio (RR) 2.9 (95% confidence interval (CI) 0.6-13.2, p= 0.25). There was no difference in OI at day 7 between the ORBCEL-C (mean (SD) 98.3 (57.2)) and placebo groups (mean (SD) 96.6 (67.3): mean difference 1.8 (95% CI 30.7-34.4, p= 0.91). There were no differences between groups in surrogate secondary outcomes (Figure 1). Clinical outcomes were underpowered, however there was no difference in mortality (28-day mortality ORBCEL-C 16.7%(n= 5), placebo 20.7%(n= 6); RR 0.8 (95% CI 0.3-2.4), p= 0.69) and an increased duration of ventilation in the ORBCEL-C group compared to placebo (ORBCEL-C 19 days (IQR 13-30), placebo 12 days (IQR 7-20); hazard ratio 0.5 (95% CI 0.3-0.9), p= 0.017).CONCLUSIONSThis phase 2 trial supports the safety of ORBCEL-C in patients with moderate to severe ARDS due to COVID-19 but did not demonstrate efficacy, and does not support routine administration of ORBCEL-C MSCs in this population. FUNDING Wellcome Trust Health Innovation Challenge Fund (reference 106939/Z/15/Z) and the Northern Ireland Health and Social Care Research and Development Fund. 1. Gorman E et al. Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial. EClinicalMedicine 2021; 41: 101167.