Management of Cytokine Storms in Severe COVID-19 Patients With Autologous Activated Platelet-rich Plasma Therapy

Study Overview
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Brief Summary
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The positive cases of coronavirus disease-2019 (COVID-19) in Indonesia has been increasing rapidly since the first case found in March 2020 to date. Coronavirus 2 (SARS-CoV-2) virus disrupts human normal immune system resulting in uncontrolled inflammatory response. Based on our research and experience in doing cell therapy for 9 years, activated platelet-rich plasma (PRP) produces anti-inflammatory effects in inflammatory condition that is beneficial for tissue regeneration. In this study, we aimed to evaluate the potential of autologous activated platelet-rich plasma (aaPRP) and the outcomes for treating severe Coronavirus Disease-2019 (COVID-19) patients in Intensive Care Unit (ICU).

Detailed Description
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PRP decreases IL-1β, IL-6, IL-8, and TNFα inflammatory genes expression while also reduces IL-1β and TNFα inflammatory cytokines production. PRP has also been showed to contain interleukin 1 receptor antagonist (IL-1RA), an anti-inflammatory cytokines that suppress IL-6 secretion.

Official Title
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Management of Cytokine Storms in Severe COVID-19 Patients With Autologous Activated Platelet-rich Plasma Therapy

Conditions
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Covid19, Sars-CoV-2 Infection, ARDS, Human, Severe covid19

Intervention / Treatment
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* Combination Product: autologous activated platelet-rich plasma
* Drug: Avigan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: severe covid-19 patient in ICU Exclusion Criteria: CKD on hemodialysis, HIV positive, hepatitis, pregnant, destroyed lung, cancer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control<br>Only received standard medication (avigan) for severe COVID-19 management | Drug: Avigan<br>* Patient received avigan 2x1,600 mg for a day, followed by 2x600 mg for five consecutive days.<br>|
| Experimental: PRP Group<br>received standard medication (avigan) for severe COVID-19 management and autologous activated platelet-rich plasma transfusion | Combination Product: autologous activated platelet-rich plasma<br>* Patient received standard medication for COVID-19 management and autologous activated platelet-rich plasma on day 1, 3 and 5 while patient in ICU. On day 0, 4 and 6, hematology analysis, multicytokines measurement and thorax X-ray were done to each patient<br>Drug: Avigan<br>* Patient received avigan 2x1,600 mg for a day, followed by 2x600 mg for five consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of aaPRP on pro-inflammatory cytokines plasma level (IL-6, IL-1B, TNFa, IFN gamma, MCP-1) before and after intervention compared to control. | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 
| to evaluate the change of Effect of aaPRP on anti-inflammatory cytokines plasma level (IL-1RA, IL-4, IL-10) before and after intervention compared to control. | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 
| Effect of aaPRP on overall adverse event related to the treatment. | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 
| Effect of aaPRP on CRP level before and after intervention compared to control. | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of aaPRP on Thorax X-ray image pre and post intervention between control and aaPRP-treated group | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 
| Effect of aaPRP on duration of hospitality of patient compared to control | Patients with positive COVID19 who will improve after receiving aaPRP compared to control. | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aaPRP, severe COVID-19, platelet-rich plasma, SARS-CoV-2, autologous