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Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)

2020年8月18日 更新者：Fu-Sheng Wang、Beijing 302 Hospital

A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients

COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.

研究概览

地位

完全的

条件

干预/治疗

详细说明

The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has unprecedentedly spread in the worldwide and been declared as a pandemic by the world health organization. COVID-19 is characterized by sustained cytokines production and hyper-inflammation, can cause clusters of severe respiratory illness with a fatality rate around 2-5%. There are currently no prophylactic vaccine and no specific antiviral treatment agents available recommended for COVID-19. Therefore, it is urgent to find a safe and effective therapeutic approach to COVID-19.

During the last decade, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. These findings seem to highlight that the beneficial effect of MSC-based treatment could be principally due by the immunomodulation and regenerative potential of these cells. MSCs could significantly reduce the pathological changes of lung and inhibit the cell-mediated immune inflammatory response induced by influenza virus in animal model . MSCs has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. Our phase I preliminary data of parallel assignment study(NCT04252118) showed that three doses of MSCs was safe in patients with COVID-19. Randomized control trial is needed to assess efficacy and safety.

The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 90 severe COVID-19 patients will be recruited in China. 60 patients will receive i.v. transfusion 3 times of MSCs (4.0*10E7 cells per time) and the standard of care as the treated group. In addition, the 30 patients will receive placebo and standard of care as control group.

Change in lesion proportion (%) of full lung volume from baseline to day 10, day28 and 90, change in consolidation/ ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90, time to clinical improvement in 28 days, mMRC (Modified Medical Research Council) dyspnea scale, 6-minute walk test, maximum vital capacity (VCmax), Diffusing Capacity (DLCO), oxygen saturation, oxygenation index, duration of oxygen therapy, side effects, immunological characteristics (immune cells, inflammatory factors, etc.) will be evaluated during the 90 days follow up.

研究类型

介入性

注册 (实际的)

100

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 中国
    • Hubei
      • Wuhan、Hubei、中国、430000
        • General Hospital of Central Theater Command
      • Wuhan、Hubei、中国、430000
        • Maternal and Child Hospital of Hubei Province
      • Wuhan、Hubei、中国、430000
        • Wuhan Huoshenshan Hospital

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 75年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Male or female, aged at 18 years (including) -75 years old
  2. Hospitalized
  3. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source
  4. Pneumonia that is judged by computed tomography
  5. In accordance with any one of the following : 1)dyspnea (RR ≥ 30 times / min), 2)finger oxygen saturation ≤ 93% in resting state, 3)arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG, 4)pulmonary imaging shows that the focus progress > 50% in 24-48 hours
  6. Interstitial lung damage is judged by computed tomography.

Exclusion Criteria:

  1. Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;
  2. Patients with malignant tumor, other serious systemic diseases and psychosis;
  3. Patients who are participating in other clinical trials;
  4. Inability to provide informed consent or to comply with test requirements.
  5. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
  6. Invasive ventilation
  7. Shock
  8. Combined with other organ failure( need organ support)
  9. Interstitial lung damage caused by other reasons ( in 2 weeks)
  10. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
生物：UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
安慰剂比较：Placebo
Participants will receive standard of care plus 3 does of placebo
生物：Saline containing 1% Human serum albumin（solution without UC-MSCs）
3 does of placebo（intravenously at Day 0, Day 3, Day 6）

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change in lesion proportion (%) of full lung volume from baseline to day 28.
大体时间：Day 28
Evaluation of Pneumonia Improvement
Day 28

次要结果测量

结果测量
措施说明
大体时间
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
大体时间：Day 10, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 90
Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
大体时间：Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
大体时间：Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Pulmonary fibrosis - related morphological features in CT scan at day 90 a. cord-like shadow b. honeycomb-like shadows c. interlobular septal thickening d. intralobular interstitial thickening e. pleural thickening
大体时间：Day 90
Evaluation of Pneumonia Improvement
Day 90
Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
大体时间：Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.
大体时间：Day 10, Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 10, Day 28, Day 90
Time to clinical improvement in 28 days.
大体时间：Day 28

Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale:

  1. Not hospitalized;
  2. Hospitalized, not requiring supplemental oxygen;
  3. Hospitalized, requiring supplemental oxygen;
  4. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
  5. Hospitalized, on invasive mechanical ventilation or ECMO;
  6. Death.
Day 28
Oxygenation index( PaO2/FiO2)
大体时间：Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
Duration of oxygen therapy(days)
大体时间：Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Blood oxygen saturation
大体时间：Day 6, Day 10, Day 28
Evaluation of Pneumonia Improvement
Day 6, Day 10, Day 28
6-minute walk test
大体时间：Day 28, Day 90
Evaluation of Pneumonia Improvement
Day 28, Day 90
Maximum vital capacity (VCmax)
大体时间：Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Diffusing Capacity (DLCO)
大体时间：Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
Evaluation of Pneumonia Improvement
Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
mMRC (Modified Medical Research Council) dyspnea scale
大体时间：Day 28, Day 90

Evaluation of Pneumonia Improvement

No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.
Day 28, Day 90
Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
大体时间：Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
大体时间：Day 6, Day 10, Day 28, Day 90
Marker of Immunological function
Day 6, Day 10, Day 28, Day 90
Adverse events
大体时间：Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
Serious adverse events
大体时间：Day 0 through Day 90
Safety endpoints
Day 0 through Day 90
All-cause mortality
大体时间：Day 0 through Day 90
Safety endpoints
Day 0 through Day 90

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Beijing 302 Hospital

合作者

Maternal and Child Health Hospital of Hubei Province
Huoshenshan Hospital
VCANBIO Cell & Gene Engineering Corporation, Ltd
The General Hospital of Central Theater Command

调查人员

  • 学习椅：Fu-Sheng Wang, MD, PhD、Beijing 302 Hospital

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2020年3月5日

初级完成 (实际的)

2020年5月12日

研究完成 (实际的)

2020年7月9日

研究注册日期

首次提交

2020年2月24日

首先提交符合 QC 标准的

2020年2月25日

首次发布 (实际的)

2020年2月28日

研究记录更新

最后更新发布 (实际的)

2020年8月19日

上次提交的符合 QC 标准的更新

2020年8月18日

最后验证

2020年8月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 2020-013-D

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

2019 年冠状病毒病（COVID-19）的临床试验

UC-MSCs的临床试验

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医疗条件

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条件

罕见疾病

药物干预

膳食补充剂

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地点

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