The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients
Overview
- Phase
- Phase 2
- Intervention
- Injection of Secretome-MSCs
- Conditions
- Covid-19
- Sponsor
- Stem Cell and Cancer Research Indonesia
- Enrollment
- 48
- Locations
- 6
- Primary Endpoint
- Change in patients clinical manifestation
- Last Updated
- 4 years ago
Overview
Brief Summary
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
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.
Investigators
Agung Putra
Assoc. Prof. Dr. dr. Agung Putra, M.Si. Med
Stem Cell and Cancer Research Indonesia
Eligibility Criteria
Inclusion Criteria
- •Patients whose clinical and laboratory test results have a positive diagnosis of Covid-
- •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
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
Arms & Interventions
Secretome-MSCs (n=24)
This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome
Intervention: Injection of Secretome-MSCs
Secretome-MSCs (n=24)
This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome
Intervention: Standard treatment of Covid-19
Control (n=24)
This group will receive standard Covid-19 therapy with the best supportive care
Intervention: Standard treatment of Covid-19
Outcomes
Primary Outcomes
Change in patients clinical manifestation
Time Frame: 1 months
mild, moderate, or severe
Need for a ventilator
Time Frame: 1 months
There are respiratory variables that made severe Covid-19 patients previously stable but worsened, requiring a ventilator Divided into two categories: 1. It is necessary 2. No need
Routine blood profile
Time Frame: 2 weeks
Obtained from patients before and after treatment
Photo thorax
Time Frame: 2 weeks
Obtained from patients before and after treatment
Blood Gas Analisis (BGA)
Time Frame: 2 weeks
Obtained from patients before and after treatment
Length of stay
Time Frame: 1 months
The length of stay from the first treatment to the patient's final outcome, recovery, or death
CRP
Time Frame: 2 weeks
Obtained from patients before and after treatment
Duration of using a ventilator
Time Frame: 1 months
Duration of use of a ventilator from the day of intubation to the day of extubation
D-dimer
Time Frame: 2 weeks
Obtained from patients before and after treatment
Secondary Outcomes
- Survival(2 months)