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

Phase 2

• Conditions: Cytokine Storm; Covid-19
• Interventions: Biological: Injection of Secretome-MSCs; Drug: Standard treatment of Covid-19

• Registration Number: NCT04753476
• Lead Sponsor: Stem Cell and Cancer Research Indonesia

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.

Study Timeline

• Study Start: 2020-06-08
• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-02-12
• Study First Posted: 2021-02-15
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-19
• Last Update Posted: 2021-05-24
• Primary Completion: 2022-02-01
• Study Completion: 2022-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 48

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Secretome-MSCs (n=24)	Injection of Secretome-MSCs	This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome
Secretome-MSCs (n=24)	Standard treatment of Covid-19	This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome
Control (n=24)	Standard treatment of Covid-19	This group will receive standard Covid-19 therapy with the best supportive care

Primary Outcome Measures

Name	Time	Method
CRP	2 weeks	Obtained from patients before and after treatment
Length of stay	1 months	The length of stay from the first treatment to the patient's final outcome, recovery, or death
Change in patients clinical manifestation	1 months	mild, moderate, or severe
Need for a ventilator	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	2 weeks	Obtained from patients before and after treatment
Photo thorax	2 weeks	Obtained from patients before and after treatment
Blood Gas Analisis (BGA)	2 weeks	Obtained from patients before and after treatment
Duration of using a ventilator	1 months	Duration of use of a ventilator from the day of intubation to the day of extubation
D-dimer	2 weeks	Obtained from patients before and after treatment

Secondary Outcome Measures

Name	Time	Method
Survival	2 months	Death

Trial Locations

Locations (6)

RSUD Bantul; 🇮🇩 Bantul, Central Java, Indonesia

Gatot Soebroto Army Hospital; 🇮🇩 Jakarta, Indonesia

RS PKU Muhammadiyah Gamping; 🇮🇩 Yogyakarta, Central Java, Indonesia

RS Primaya Bekasi Timur; 🇮🇩 Bekasi, Jakarta, Indonesia

Bhayangkara Hospital; 🇮🇩 Makassar, South Celebes, Indonesia

Dr. Esnawan Antariksa Air Force Hospital; 🇮🇩 Jakarta, Indonesia