Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome

Study Overview
=================
Brief Summary
-----------------
Corona virus disease 2019 (COVID-19) has been declared as a Pandemic by the World Health Organization (WHO). According to WHO report on March 31st 2020, globally COVID-19 have infected over 750,000 people and caused over 36,000 deaths with case fatality rate of 4.85%. In Indonesia, COVID-19 have infected 1,414 people and caused 122 deaths with case fatality rate of 8.63%. In severe cases, COVID-19 causes complications, such as acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ dysfunction syndrome (MODS), where age and comorbid illnesses as a major factor to these complications. Up to this point there are several promising therapies for COVID-19 but is not yet recommended and in need of further research. The use of convalescent plasma has been approved by the US Food and Drug Administration (FDA) through the scheme of emergency investigational new drug (eIND). This method has been used as the treatment in several outbreak or plague cases over the years, such as the flu epidemic in 1918, polio, measles, mumps, SARS (severe acute respiratory syndrome), EVD (Ebola virus disease) and MERS (middle-eastern respiratory syndrome) and this treatment shows better outcome. Several case report on the use of convalescent plasma for COVID-19 patients with ARDS and mechanical ventilation has been reported and shows promising outcome. Nevertheless, larger and multicenter research need to be done to assess and evaluate the effectiveness and safety of convalescent plasma therapy on for COVID-19 patients with ARDS.

Official Title
-----------------
Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome in Referral Hospitals in Indonesia

Conditions
-----------------
COVID, Acute Respiratory Distress Syndrome

Intervention / Treatment
-----------------
* Biological: Convalescent plasma
* Drug: Standard of care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged more than equal to 18 years. COVID-19 confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) Having severe pneumonia. PAO2 / FIO2 <300. Exclusion Criteria: Contraindication to blood transfusions (fluid overload, history of anaphylaxis of blood products) Multiple and severe organ failure, hemodynamically unstable Other uncontrolled infections Disseminated intravascular coagulation (DIC) which requires a replacement factor/FFP Hemodialysis patients or CRRT (continuous renal replacement therapy) Active intracranial bleeding Significant myocardial ischemia Receiving tocilizumab treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: convalescent plasma and standard of care<br> | Biological: Convalescent plasma<br>* Convalescent plasma of recovered COVID-19 patients (donor)<br>Drug: Standard of care<br>* According to national or hospital guidelines COVID-19 Management Protocol<br>|
| Active Comparator: standard of care<br> | Drug: Standard of care<br>* According to national or hospital guidelines COVID-19 Management Protocol<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Proportion of all-cause mortality | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay in intensive care unit | Mean length of stay in intensive care unit | up to 28 days | 
| Duration of mechanical ventilation | Mean duration of mechanical ventilation | up to 28 days | 
| Body temperature (degree in Celsius) | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| The Sequential Organ Failure Assessment (SOFA) Score | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| PAO2/FIO2 ratio | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| C-Reactive Protein (CRP) in mg/L | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| D-Dimer in ng/mL | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| Procalcitonin in ng/mL | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| Interleukin 6 (IL-6) in pg/mL | Mean change from baseline using time series analysis | Day 1, 3, 5, and 7 after administration of therapy | 
| Allergic/ anaphylaxis transfusion reaction | Number of participants with allergic/ anaphylaxis transfusion reaction | 24 hours post-transfusion | 
| Hemolytic transfusion reaction | Number of participants with Hemolytic transfusion reaction | 24 hours post-transfusion | 
| Transfusion Related Acute Lung Injury | Number of participants with Transfusion Related Acute Lung Injury | 24 hours post-transfusion | 
| Transfusion associated Circulatory Overload | Number of participants with Transfusion associated Circulatory Overload | 24 hours post-transfusion |