Clinical trial NCT04753476: Treatment of Severe COVID-19 Patients Using Secretome of Hypoxia-Mesenchymal Stem Cells in Indonesia
Official title: The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid-19
Cytokine Storm
Keywords: secretome
mesenchymal stem cells
covid-19
hypoxia
Lead sponsor: Stem Cell and Cancer Research Indonesia
Sponsor class: NETWORK
Collaborators: name: Provincial Government of Central Java, Indonesia
First posted: 2021-02-15
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Patients whose clinical and laboratory test results have a positive diagnosis of Covid-19.
2. Patients who are willing to participate as subjects in the study by signing the informed content.
3. Criteria for Berlin to enter ARDS (moderate and severe) with or without a ventilator:

   * PaO2 / FiO2: moderate 100-200
   * PaO2 / FiO2: severe \<100
4. One or more comorbid history
5. SOFA score

Exclusion Criteria:

1. The Covid19 patient has fibrosis (based on the results of the chest X-ray or CT chest)
2. ECOG 4 performance status, decreased irreversible consciousness, brain stem death.
3. Severe NYHA III / IV heart failure
4. Pregnant women

Primary outcomes:
measure: Change in patients clinical manifestation
timeFrame: 1 months
measure: Need for a ventilator
timeFrame: 1 months
measure: Duration of using a ventilator
timeFrame: 1 months
measure: Length of stay
timeFrame: 1 months
measure: Routine blood profile
timeFrame: 2 weeks
measure: CRP
timeFrame: 2 weeks
measure: D-dimer
timeFrame: 2 weeks
measure: Blood Gas Analisis (BGA)
timeFrame: 2 weeks
measure: Photo thorax
timeFrame: 2 weeks
Secondary outcomes:
measure: Survival
timeFrame: 2 months
Other outcomes:
Locations:
city: Bantul
country: Indonesia
facility: RSUD Bantul
state: Central Java
city: Yogyakarta
country: Indonesia
facility: RS PKU Muhammadiyah Gamping
state: Central Java
city: Bekasi
country: Indonesia
facility: RS Primaya Bekasi Timur
state: Jakarta
city: Makassar
country: Indonesia
facility: Bhayangkara Hospital
state: South Celebes
city: Jakarta
country: Indonesia
facility: Gatot Soebroto Army Hospital
city: Jakarta
country: Indonesia
facility: Dr. Esnawan Antariksa Air Force Hospital
Study officials:
affiliation: Stem Cell and Cancer Research Indonesia
name: Agung Putra, Assoc.Prof
role: PRINCIPAL_INVESTIGATOR
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