Statistical and Epidemiological Study Based on the Use of Convalescent Plasma for the Management of Patients With COVID-19

Study Overview
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Brief Summary
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The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission. SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus. The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

Detailed Description
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The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission. SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus. The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

Official Title
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Pilot Clinical, Statistical and Epidemiological Study on Efficacy and Safety of Convalescent Plasma for the Management of Patients With COVID-19

Conditions
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COVID-19 Pneumonia, Convalescent Plasma

Intervention / Treatment
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* Biological: Convalescent plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Donors): Signed informed consent At least positive for 1 q-PCR test for SARS-CoV-2 14 days of COVID-19 clinical remission Positive serologic test for SARS-CoV-2 Requirements to donate according to NOM-253-SSA1-2012 To accept sample storing for future study Inclusion Criteria (Receptors): Signed informed consent provided by the patient, legal guardian or the health provider if not available Patients hospitalized in an ICU dedicated to the treatment of COVID-19 patients At least positive for 1 q-PCR test for SARS-CoV-2 Patients with COVID-19 defined as severe or critically ill: Severe: RF > 30 bpm, oxygen saturation <94%, Pa/FiO2 <301, bilateral lung infiltrates that extends in >50% (by chest radiograph or CT scan) in 24-48 hours Critically ill: Respiratory failure (PaO2 <60 mmHg or SatO2 <90% with FiO2 >60%) and septic shock (MAP <65 mmHg with vasoactive requirement, lactate > 2 mmol/L and SOFA score >1) Exclusion Criteria: Positive pregnancy test Patients in lactation Informed consent not signed Patients involved in other treatment protocols Patients on immunomodulatory drugs (DMARDs, monoclonal antibodies or smal molecule drugs)

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: Pilot, experimental, randomized, prospective, longitudinal, clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent plasma<br>Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval. | Biological: Convalescent plasma<br>* Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval.<br>|
| Placebo Comparator: Best available treatment<br>Best available treatment + Placebo (0.9% saline solution) Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Placebo will consist on 2 doses of 200 ml of 0.9% saline solution separated on a 12 hour interval. | Biological: Convalescent plasma<br>* Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Any cause mortality during the first 30 days of treatment | 30 days | 
| Side effects | Side effects associated with the administration of convalescent plasma | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay in Intensive Care Unit (ICU) | Time to discharge from the ICU | 14 days | 
| Length of stay in hospitalization | Time for discharge from hospital | 21 days | 
| Days of mechanical ventilation | Number of days with ventilatory support | 14 days | 
| Inflammatory biomarkers (d-dimer) | change in D-dimer (micrograms/L) | 21 days | 
| Inflammatory biomarkers (c-reactive protein) | change in C-reactive protein (milligrams/dL) | 21 days | 
| Inflammatory biomarkers (lactate dehydrogenase) | Change in LDH (UI/L) | 21 days | 
| Inflammatory biomarkers (ferritin) | Change in ferritin (nanograms/mL) | 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Convalescent plasma, plasmapheresis