PURPOSE Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS). METHODS This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in patients with moderate-to-severe ARDS in 12 UK and USA centres. Cohorts 1 and 2 were open-label, evaluating acute safety in three subjects receiving 300 or 900 million cells, respectively. Cohort 3 was a randomised, double-blind, placebo-controlled parallel trial infusing 900 million cells (n = 20) or placebo (n = 10) within 96 h of ARDS diagnosis. Primary outcomes were safety and tolerability. Secondary endpoints included clinical outcomes, quality of life (QoL) and plasma biomarkers. RESULTS No allergic or serious adverse reactions were associated with cell therapy in any cohort. At baseline, the cohort 3 cell group had less severe hypoxia. For cohort 3, 28-day mortality was 25% for cell vs. 45% for placebo recipients. Median 28-day free from intensive care unit (ICU) and ventilator-free days in the cell vs. placebo group were 12.5 (IQR 0,18.5) vs. 4.5 (IQR 0,16.8) and 18.5 (IQR 0,22) vs. 6.5 (IQR 0,18.3), respectively. A prospectively defined severe ARDS subpopulation (PaO2/FiO2 < 150 mmHg (20 kPa); n = 16) showed similar trends in mortality, ICU-free days and ventilator-free days favouring cell therapy. Cell recipients showed greater recovery of QoL through Day 365. CONCLUSIONS Multipotent adult progenitor cells were safe and well tolerated in ARDS. The clinical outcomes warrant larger trials to evaluate the therapeutic efficacy and optimal patient population.

中文翻译：

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多能成人祖细胞在急性呼吸窘迫综合征 (MUST-ARDS) 中的安全性和有效性：一项多中心、随机、双盲、安慰剂对照的 1/2 期试验。

目的骨髓来源的同种异体多能成体祖细胞在急性呼吸窘迫综合征 (ARDS) 的临床前模型中证明了安全性和有效性。方法 该 1/2 期试验评估了在英国和美国 12 个中心的中度至重度 ARDS 患者中静脉注射多能成人祖细胞的安全性和耐受性。第 1 组和第 2 组是开放标签的，评估分别接受 300 或 9 亿细胞的三名受试者的急性安全性。队列 3 是一项随机、双盲、安慰剂对照的平行试验，在 ARDS 诊断后 96 小时内注入 9 亿个细胞（n = 20）或安慰剂（n = 10）。主要结果是安全性和耐受性。次要终点包括临床结果、生活质量 (QoL) 和血浆生物标志物。结果 在任​​何队列中均未出现与细胞疗法相关的过敏或严重不良反应。在基线时，队列 3 细胞组的缺氧程度较低。对于队列 3，细胞组的 28 天死亡率为 25%，安慰剂组为 45%。与安慰剂组相比，细胞与安慰剂组的中位 28 天免于重症监护病房 (ICU) 和无呼吸机天数分别为 12.5 (IQR 0,18.5) 与 4.5 (IQR 0,16.8) 和 18.5 (IQR 0,22) 与. 6.5 (IQR 0,18.3)，分别。前瞻性定义的严重 ARDS 亚群（PaO2/FiO2 < 150 mmHg (20 kPa)；n = 16）在死亡率、无 ICU 天数和无呼吸机天数方面显示出相似的趋势，有利于细胞疗法。细胞接受者在第 365 天显示出更好的 QoL 恢复。结论 多能成人祖细胞在 ARDS 中是安全且耐受性良好的。