同种异体间充质基质细胞治疗中重度急性呼吸窘迫综合征：一项双盲、安慰剂对照、多中心2b期临床试验（STAT）
Treatment with Allogenic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multi-Center, Phase 2b Clinical Trial (STAT).
作者信息
Matthay Michael A, Zhou Hanjing, Sarma Aartik, Alipanah-Lechner Narges, Hendrickson Carolyn, Kornblith Lucy Z, Schreiber Martin, Zonies David, Khan Akram, Robinson Bryce, Johnson Nicholas J, Ware Lorraine B, Guillamondegui Oscar, Casey Jonathan, Moore Laura, Patel Bela, Kao Lillian, Wade Charles E, Fox Erin, Cox Charles, Khawanja Farrakh, Aguillon Prada Robier, Hossri Sami, Callcut Rachael, Albertson Timothy, Delucchi Kevin L, McMillan Melanie, Langelier Charles R, Pati Shibani, McKenna David H, Leroux Carolyn, Calfee Carolyn S, Liu Kathleen D
机构信息
Cardiovascular Research Institute (CVRI), University of San Francisco, Medicine and Anesthesia, San Francisco, California, United States;
University of California, San Francisco, Cardiovascular Research Institute, San Francisco, California, United States.
出版信息
Am J Respir Crit Care Med. 2025 Jul 29. doi: 10.1164/rccm.202411-2254OC.
BACKGROUND
Prior clinical trials established the safety, but not the efficacy of bone marrow-derived mesenchymal stromal cells (MSCs) in the acute respiratory distress syndrome (ARDS).
METHODS
We conducted a prospective, double-blind, multi-center randomized phase 2b clinical trial of one dose of intravenous MSCs (10 x 10/kg predicted body weight) versus placebo in 120 ventilated patients with ARDS (PaO/FiO < 250 mmHg). The primary endpoint was change in oxygenation index (OI) over 36 hours from baseline.
FINDINGS
Enrollment began in January 2020. Due to the Coronavirus 2019 (COVID-19) pandemic, the majority of subjects (101/120, 84%) developed ARDS from COVID-19. There were no significant baseline differences in severity of illness between patients treated with MSCs and those who received placebo in the entire cohort of 120 patients or in the 101 patients with COVID-19 ARDS. There was no difference in the primary endpoint of change in oxygenation index from baseline over 36 hours after study product administration for the entire cohort or the COVID-19 subgroup, nor were there significant differences in mortality at 14, 28, 60 or 180 days. Plasma protein biomarker and gene expression analyses identified sub-groups of patients with differential treatment responses in terms of clinical outcomes.
INTERPRETATION
This phase 2b clinical trial identified no physiologic or clinical benefit from a single dose of MSCs in patients with ARDS, including those with COVID-19 ARDS. In future trials, baseline plasma biological markers may help identify patients who are more likely to benefit from MSCs therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.
CLINICALTRIALS
gov, ID: NCT03818854.
背景
先前的临床试验证实了骨髓间充质基质细胞（MSCs）用于急性呼吸窘迫综合征（ARDS）的安全性，但未证实其有效性。
方法
我们进行了一项前瞻性、双盲、多中心2b期随机临床试验，在120例机械通气的ARDS患者（动脉血氧分压/吸入氧浓度<250 mmHg）中，对比一剂静脉注射MSCs（10×10/kg预计体重）与安慰剂的效果。主要终点是从基线开始36小时内氧合指数（OI）的变化。
研究结果
入组于2020年1月开始。由于2019冠状病毒病（COVID-19）大流行，大多数受试者（101/120，84%）因COVID-19患上ARDS。在120例患者的整个队列中，或在101例COVID-19 ARDS患者中，接受MSCs治疗的患者与接受安慰剂治疗的患者在疾病严重程度方面无显著基线差异。在整个队列或COVID-19亚组中，研究产品给药后36小时内，从基线开始的氧合指数变化这一主要终点无差异，在14、28、60或180天的死亡率也无显著差异。血浆蛋白生物标志物和基因表达分析确定了在临床结局方面有不同治疗反应的患者亚组。
解读
这项2b期临床试验未发现一剂MSCs对ARDS患者（包括COVID-19 ARDS患者）有生理或临床益处。在未来试验中，基线血浆生物标志物可能有助于识别更可能从MSCs治疗中获益的患者。本文为开放获取文章，根据知识共享署名非商业性无衍生作品许可协议4.0（http://creativecommons.org/licenses/by-nc-nd/4.0/）分发。临床试验注册信息可在www.CLINICALTRIALS.gov查询，编号：NCT03818854。
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