Inactivated Convalescent Plasma as a Therapeutic Alternative in Patients CoViD-19

Study Overview
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Brief Summary
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Convalescent plasma is a way to provide passive immunity to a person exposed to an infectious agent. It has been used as a therapeutic tool for emerging viral infections without specific treatment and with high morbidity and mortality, such as Influenza H1N1, H5N1, H7N9, Ebola, MERS, SARS-CoV1, and even SARS-Cov2, with satisfactory results regarding evolution clinic of patients treated and without significant adverse events reported. One of its main advantages of convalescent plasma is to generate a rapid immune response (even faster than a vaccine), against a pathogen that circulates in a specific geographic area, probably common for both donor and recipient.

Detailed Description
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This study consists of obtaining convalescent plasma by means of apheresis, from recovered donors, who meet the eligibility criteria to donate. Then this plasma will be inactivated by riboflavin and UV based photochemical treatment (Mirasol technology - Terumo BCT®), in order to add more transfusion security to the procedure. Finally, it will be transfused to CoViD-19 patients hospitalized in any of the participating clinics. There are currently no reported significant adverse events associated with this therapy. Have been published two serial cases reports,more evidence is necessary to standardize the treatment.

Official Title
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Inactivated Convalescent Plasma as a Therapeutic Alternative in Hospitalized Patients CoViD-19

Conditions
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Infections, Coronavirus

Intervention / Treatment
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* Drug: Inactivated convalescent plasma
* Drug: Support treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years old Confirmed laboratory diagnosis for qRT-PCR to SARS-CoV-2 Meet any of the following medical criteria (Defined by WHO): Be currently hospitalized with: Pneumonia, Severe pneumonia, Acute Respiratory Distress Syndrome (moderate or severe), Sepsis or Septic shock The patient, or his representative, must sign an informed consent Exclusion Criteria: Participate in another clinical trial for CoViD- 19 History of acute allergic transfusion reactions due to transfusion of blood or other components, especially plasma components (fresh frozen plasma, cryoprecipitate and platelets), History of allergic reaction due to IgA deficiency Allergic reaction to sodium citrate or riboflavin (vitamin B2) History of immunosuppression

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: MULTICENTER, CONTROLLED, RANDOMIZED, SIMPLE BLIND, CLINICAL TRIAL
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent plasma+Support treatment selected by the hospital<br>Participants will receive two doses of ABO - Rh compatible inactivated convalescent plasma, each one of 200 mililiters (mL), with a 24-hour interval via transfusion, for a final volume of 400 mL, meanwhile they continue to receive the supportive treatment chosen by the hospitals, according to each institutional protocol. | Drug: Inactivated convalescent plasma<br>* Day 0: Transfusion of 200mL of ABO -Rh compatible inactivated convalescent plasma, Start of support treatment selected by medical staff according to each institutional protocol Day 1: Transfusion of 200mL of ABO -Rh compatible inactivated convalescent plasma<br>* Other names: Inactivated convalescent plasma SARS-Cov-2 + Support treatment;Drug: Support treatment<br>* Day 0: Start of support treatment selected by medical staff according to each each institutional protocol<br>* Other names: Support treatment under medical decision;|
| Active Comparator: Support treatment selected by the hospital<br>The best support treatment selected by the hospital, according to each institutional protocol. Due to the ongoing development of knowledge of pathophysiology and scientific evidence of the available alternatives, it will be selected at the time of treatment. | Drug: Support treatment<br>* Day 0: Start of support treatment selected by medical staff according to each each institutional protocol<br>* Other names: Support treatment under medical decision;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality reduction in CoViD-19 patients treated with inactivated convalescent plasma + support treatment | To assess the efficacy in reducing mortality in CoViD-19 patients treated with inactivated convalescent plasma together with the support treatment selected by the respective hospital | Over a period of 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evolution | Number of Participants with resolution of fever (<38ºC temperature) | Over a period of 28 days | 
| Clinical evolution by seven-parameter ordinal scale | The clinical improvement will be established with a two-point improvement within this seven categories (recommended by World Organization Health-WHO): 1) Not hospitalized, with resumption of normal activities 2) Not hospitalized, but unable to resume normal activities 3) Hospitalized that does not require supplemental oxygen 4) Hospitalized requiring supplemental oxygen 5) Hospitalized requiring high-flow nasal oxygen therapy, non-invasive mechanical ventilation, or both 6) Hospitalized requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both 7) death | 3, 7, 14 and 28 days | 
| Multi-organ failure progression | Evolution by SOFA (Sequential Organ Failure Assessment), The range is between 0 and 24 points, with the highest scores being indicators of a more serious illness | 3, 7, 14 and 28 days | 
| Change in hemoglobin concentration | Compare the change in hemoglobin concentration at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in blood cell count | Compare the change in blood cell count at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in serum creatinine level | Compare the change in Serum creatinine concentration at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in aspartate aminotransferase level | Compare the change in aspartate aminotransferase level at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in alanin aminotransferase level | Compare the change in Alanine aminotransferase levels at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in bilirubin level | Compare the change in bilirubin levels at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in lactate dehydrogenase level | Compare the change in lactate dehydrogenase levels at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in creatine kinase level | Compare the change in creatine kinase levels at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in creatine kinase MB level | Compare the change in creatine kinase MB levels at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in C reactive protein concentration | Compare the change in C reactive protein concentration at 3, 7, 14 and 28 days after treatment, in mg/L | 3, 7, 14 and 28 days | 
| Change in D Dimer concentration | Compare the change in D Dimer concentration at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in Procalcitonin concentration | Compare the change in procalcitonin concentration at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Change in IL6 level | Compare the change in IL6 level at 3, 7, 14 and 28 days after treatment | 3, 7, 14 and 28 days | 
| Radiography imaging | Resolution of chest radiography imaging findings (example, bilateral, peripheral and basal predominant ground-glass opacity, consolidation, or both) | Over a period of 60 days | 
| Tomography imaging | Resolution of tomography imaging (example, patches located in the subpleural regions of the lung) | Over a period of 60 days | 
| Assessment of oxygenation | Arterial oxygen partial pressure (PaO2) in mmHg / Inspired fraction of oxygen (FIO2) ratio | 3, 7, 14 and 28 days | 
| Viral Load | Viral Load Quantification | 0, 3, 7 days and until hospital discharge or a maximum of 60 days whichever comes first | 
| Antibody titer | Neutralizing antibody anti SARS-CoV-2 titer evolution | Day 0, Day 3 and Day 7 | 
| Oxygen-free days through Day 60 | Number of days without use of Oxygen | Until hospital discharge or a maximum of 60 days whichever comes first | 
| Mechanical ventilation-free days through Day 28 | Number of days without use of mechanical ventilation | Until hospital discharge or a maximum of 28 days whichever comes first | 
| Intensive Care Unit (ICU)-free days through Day 28 | Time outside of ICU, in days | Until hospital discharge or a maximum of 28 days whichever comes first | 
| Hospital-free days through Day 60 | Time outside of the hospital, in days | Until hospital discharge or a maximum of 60 days whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CoViD-19, Pathogen inactivation, Apheresis, Convalescent plasma