Treatment of Severe COVID-19 Patients Using Secretome of Hypoxia-Mesenchymal Stem Cells in Indonesia

Study Overview
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Brief Summary
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In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated with secretome of hypoxia-mesenchymal stem cells. The improvement in clinical, laboratory, and radiological manifestations will be evaluated in treated patients compared with the control group.

Detailed Description
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The devastating effect of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) infection is caused by a robust cytokine storm that leads to lung tissue damage. Several studies reported a correlation between disease severity and the release of excessive proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-6, IL-1, IFN-Υ, IFN-Υ-induced protein 10 (IP10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a), and granulocyte-colony stimulating factor (G-CSF). This finding was confirmed by the high level of plasma cytokines found in most severe COVID-19 patients associated with extensive lung damage. Therefore, finding an effective therapeutic option to control the devastating cytokine storm of COVID-19 and regenerate the damaged lung is crucial. Previous studies reported that the hypoxic condition of MSCs could enhance the release of their active soluble molecules known as Secretome-MSCs (S-MSCs), such as IL-10 and TGF-β that useful in alleviating inflammation. Moreover, they could also increase the expression of growth factors such as VEGF and PDGF that accelerate lung injury improvement. These active molecules could potentially serve as a biological therapeutic agent for treating the severe SARS-CoV-2 infection. According to recent studies, we successfully isolated the S-MSCs from their culture medium using tangential flow filtration (TFF) strategy with several molecular weight cut-off category. This study investigated the clinical outcomes of severe COVID-19 patients with several comorbidities treated with S-MSCs in Indonesia.

Official Title
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The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients

Conditions
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Covid-19, Cytokine Storm

Intervention / Treatment
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* Biological: Injection of Secretome-MSCs
* Drug: Standard treatment of Covid-19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients whose clinical and laboratory test results have a positive diagnosis of Covid-19. Patients who are willing to participate as subjects in the study by signing the informed content. Criteria for Berlin to enter ARDS (moderate and severe) with or without a ventilator: PaO2 / FiO2: moderate 100-200 PaO2 / FiO2: severe <100 One or more comorbid history SOFA score Exclusion Criteria: The Covid19 patient has fibrosis (based on the results of the chest X-ray or CT chest) ECOG 4 performance status, decreased irreversible consciousness, brain stem death. Severe NYHA III / IV heart failure Pregnant women
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 |
| --- | --- |
| Experimental: Secretome-MSCs (n=24)<br>This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome | Biological: Injection of Secretome-MSCs<br>* Injection of Hypoxic Secretome-MSCs intramuscular (deltoideus) : Day 1: 1 cc every 12 hours Day 2: 1 cc every 12 hours Day 3: 1 cc every 12 hours<br>Drug: Standard treatment of Covid-19<br>* Patients will be given Standard treatment of Covid-19 which accordance with National protocol<br>|
| Other: Control (n=24)<br>This group will receive standard Covid-19 therapy with the best supportive care | Drug: Standard treatment of Covid-19<br>* Patients will be given Standard treatment of Covid-19 which accordance with National protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patients clinical manifestation | mild, moderate, or severe | 1 months | 
| Need for a ventilator | There are respiratory variables that made severe Covid-19 patients previously stable but worsened, requiring a ventilator Divided into two categories: It is necessary No need | 1 months | 
| Duration of using a ventilator | Duration of use of a ventilator from the day of intubation to the day of extubation | 1 months | 
| Length of stay | The length of stay from the first treatment to the patient's final outcome, recovery, or death | 1 months | 
| Routine blood profile | Obtained from patients before and after treatment | 2 weeks | 
| CRP | Obtained from patients before and after treatment | 2 weeks | 
| D-dimer | Obtained from patients before and after treatment | 2 weeks | 
| Blood Gas Analisis (BGA) | Obtained from patients before and after treatment | 2 weeks | 
| Photo thorax | Obtained from patients before and after treatment | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Death | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secretome, mesenchymal stem cells, covid-19, hypoxia