DW-MSC 输注治疗低临床风险 COVID-19 感染患者的安全性：一项随机、双盲、安慰剂对照试验。
Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial.
机构信息
National Institute of Health and Research Development, Ministry of Health, Republic of Indonesia (NIHRD, MoH RI), Jakarta, Indonesia.
RSUP Dr. Wahidin Sudirohusodo, Pulmonology and Respiratory Medicine, Medical Faculty, Hasanuddin University, Makassar, Indonesia.
出版信息
Stem Cell Res Ther. 2022 Apr 1;13(1):134. doi: 10.1186/s13287-022-02812-4.
BACKGROUND
Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection.
METHODS
This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 10 cells and 1.0 × 10 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period.
RESULTS
There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups.
CONCLUSIONS
Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856.
背景
由于间充质干细胞（MSCs）具有免疫调节特性，因此有人提出它们具有治疗潜力，可以改善 COVID-19 患者的临床结局。然而，非重症 COVID-19 感染患者输注 MSCs 的安全性和疗效特征尚未完全确定；特别是，在低临床风险 COVID-19 感染患者的 MSC 输注剂量依赖性研究方面，文献中存在很大的空白。
方法
这是一项 1 期、双盲、安慰剂对照、随机临床试验，研究了低剂量（DW-MSC）两种剂量（高和低）在低临床风险 COVID-19 患者中的安全性、可行性和耐受性。本研究共纳入 9 例患者，并随机分为低剂量（TL）、高剂量（TH）和安慰剂（C）组。TL 和 TH 组患者分别单次静脉输注 5.0×10 个细胞和 1.0×10 个细胞。主要终点是 28 天研究期间发生的治疗后不良事件（TEAE）。在观察期间，每周还监测生命体征和各种炎症标志物。
结果
在基线时，各组（TL、TH 和 C）的临床特征无明显差异。所有患者在研究期间均未出现病情加重。在研究过程中，5 例患者共发生 6 例 TEAE，但均不严重。随访期间，8 例患者康复出院，无并发症。1 例患者在研究结束时出现肝功能标志物异常。整个临床过程中，各组炎症标志物的变化差异不大。
结论
本临床试验提供了 MSCs 治疗低临床风险 COVID-19 患者的安全性可靠结果。然而，进一步确认 MSC 的治疗效果方面需要在 COVID-19 严重程度不同的患者中进行大规模随机对照试验。
试验注册
ClinicalTrials.gov，NCT04535856。2020 年 9 月 2 日注册，https://clinicaltrials.gov/ct2/show/NCT04535856。
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