UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia

Study Overview
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Brief Summary
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The goal of this randomized, controlled, open-labeled interventional clinical trial is to test the efficacy and safety of umbilical cord mesenchymal stem cells (UC- MSCs) in the treatment of severe and critical COVID-19 patients with refractory hypoxia even after sufficient standard treatment according to the tenth edition of Chinese guidelines for COVID-19 infection. The main questions it aims to answer are: 1. The efficacy of UC-MSCs in the treatment of severe and critical COVID-19 patients with refractory hypoxia. 2. The safety of UC-MSCs in the treatment of severe and critical COVID-19 patients. 3. The potential immune mechanisms of UC- MSCs in the treatment of severe and critical COVID-19 patients. Participants will receive standard therapy, or the UC-MSCs treatment. For the standard treatment, it will be conducted according the 10th edition of Chinese guidelines for severe or critical COVID-19 infection. For UC-MSCs treatment, participants will be given UC-MSCs instillation at the first and fourth day after assignment. Blood examples will be taken at indicated time for arterial blood gas analysis and other tests. And participants should also objectively report their symptoms change and other information related to the treatment as listed the research protocol.

Official Title
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Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe and Critical COVID-19 With Refractory Hypoxia

Conditions
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Mesenchymal Stem Cell, COVID-19 Pneumonia

Intervention / Treatment
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* Biological: UC-MSCs treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age ranges from 18 to85 (inclusive), regardless of gender. Patients who still have refractory hypoxia after sufficient standard treatment for severe and critical COVID-19 pneumonia following the suggestion of the Chinese diagnostic criteria for COVID-19 pneumonia in the Diagnosis and Treatment Plan for COVID-19 Pneumonia (Tentative tenth Edition). 20kg/m2≤body mass index(BMI)≤30 kg/m2. Volunteer to participate in this clinical study and sign the written informed consent Exclusion Criteria: Those who are using immunosuppressive drugs or long-term immunosuppressive drugs after organ transplantation. T lymphocyte abnormality (allogeneic may be considered, depending on clinical opinion), HIV positive. Highly allergic or have a history of severe allergy, especially Interleukin-2 allergy. Pregnant and lactating women. Patients with severe autoimmune disease history; Allergies to all biological reagents in this treatment, such as Interleukin-2. Patients with serious complications, including chronic cardiac insufficiency (NYHA cardiac function grading assessment of cardiac function grade III - IV), chronic renal insufficiency (CKD stage 3 and above); Chronic liver insufficiency (Child-Pugh score>7); Patients with malignant tumors. Patients with pulmonary embolism or acute coronary syndrome. Patients with severe organ dysfunction caused by other diseases. There are other situations that the researcher thinks are not suitable to participate in this clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>Participants will receive standard therapy, including oxygen therapy，glucocorticoid and other antiinflammatory drugs and supportive treatments according the ninth edition of Chinese guidelines for the treatment of COVID-19 infection. | |
| Experimental: UC-MSCs treatment<br>Participants will receive two doses of UC-MSCs instillation at the first and fourth day after the assignment on the basis of standard treatment. | Biological: UC-MSCs treatment<br>* Participants will receive two doses of UC-MSCs treatment, each dose will contain 1*10^6 cells/kg suspended in 100 ml albumin solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation index | Oxygenation index is the artery partial pressure of oxygen divided by the concentration of inhaled oxygen. | Change from baseline Oxygenation index (PaO2/FiO2) at 1,3,7,14,28 (or before the day of discharge if participants discharge within 28 days) days after the treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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umbilical cord mesenchymal stem cells, covid-19 pneumonia, refractory hypoxia