Convalescent Plasma (PC) and Human Intravenous Anti-COVID-19 Immunoglobulin (IV Anti COVID-19 IgG) in Patients Hospitalized for COVID-19.

Study Overview
=================
Brief Summary
-----------------
A randomized, open-label, multicenter, three-arm clinical trial to study the efficacy and safety of passive immunotherapy (convalescent plasma and anti-COVID-19 human immunoglobulin) compared to the standard treatment in Colombia.

Detailed Description
-----------------
The study population will be patients (≥18 years) hospitalized by COVID-19 but still with an early form of the disease (in states 1-3 of the ordinal scale) who do not require mechanical ventilation (invasive or non-invasive) and who can give their consent informed. All the participants will receive non-specific supportive treatment for COVID-19 such as oxygen, IV liquid or corticosteroids. Additionally, they will be randomized to one of the following arms: Experimental arm 1: Plasma with inactivation/reduction of pathogens from convalescent patients with COVID-19 and who at the same time receive support therapy, in the 200 - 250 mL scheme, on days 1 and 3 of the intervention. Experimental arm: Anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S, intravenous at a dose of immunoglobulin 10% IgG solution (10% mL vial) for: Patient of 50 Kg or more, a dose of 50 mL will be applied on days 1 and 3 of treatment. Patients of less than 50 Kg, the dose will be 1 mL / Kg, will be applied on days 1 and 3 of treatment. This arm will be included once available. The supply of anti-COVID-19 human immunoglobulin produced by LifeFactors will be carried out once the national regulatory agency (Invima) grants authorization and/or the regulatory requirements for the production of medications are met. Control arm: Standard (specific) therapy for COVID-19 according to the suggested pharmacological recommendations of the Colombian Association of Infectious Diseases - ACIN. This therapy is subject to changes that are determined by the Colombian Health Regulatory Authorities.

Official Title
-----------------
A Randomized, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of the Use of Convalescent Plasma (PC) and Human Intravenous Anti COVID-19 Immunoglobulin (IV Anti COVID-19 IgG) in Patients Hospitalized for COVID-19.

Conditions
-----------------
Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
-----------------
* Biological: COVID-19 convalescent plasma
* Biological: Anti-COVID-19 human immunoglobulin
* Drug: Standard (specific) therapy for COVID-19


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obtaining the informed written consent before carrying out the study procedures, by the patients. Adult patients ≥18 years at the time of recruitment for the study. Patients with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction on nasal/oropharyngeal swabs or any other relevant specimen <72 hours before randomization. Patients requiring hospitalization for COVID-19 without mechanical ventilation (invasive or non-invasive, including an oxygen mask with reserve bag) and at least one of the following: Radiographic evidence of pulmonary infiltrates by images (chest radiography, computed tomography, etc.), Clinical evaluation (evidence of rales/crackles on examination) and oxygen saturation ≤ 94% in ambient air requiring supplemental oxygen. Patient with no more than 72 hours (3 days) of hospitalization prior to the administration of PC treatment (except the days after initial hospital admission for other reasons and prior to COVID-19 infection). Patients who do not have more than 10 days between the onset of symptoms (fever or cough) and the day of administration of treatment or the demonstration of the absence of anti-SARS-CoV-2 antibodies (patients with more than 10 days of symptoms they can only be included if a negative antibody result has been confirmed). Exclusion Criteria: Patient in a state of pregnancy. Require mechanical ventilation (invasive or non-invasive, including oxygen mask with reserve bag) on examination. Participation in any other clinical trial of an experimental treatment for COVID-19. At the discretion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, regardless of the provision of treatments. Any incompatibility or allergy to the administration of plasma of human origin. Severe chronic kidney disease in stage 4 or requiring dialysis (that is, glomerular filtration rate <30). Any condition that in the investigator's opinion limits participation in the study.

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<br>Plasma from patients recovering from COVID-19. | Biological: COVID-19 convalescent plasma<br>* Plasma from convalescent patients with COVID-19 and at the same time receiving supportive therapy, with inactivation / reduction of pathogens, in the scheme of two doses of 200 - 250 mL administered on days 1 and 3 of the intervention.<br>|
| Experimental: Anti-COVID-19 human immunoglobulin<br>Anti-COVID-19 human immunoglobulin to be administered intravenously. | Biological: Anti-COVID-19 human immunoglobulin<br>* Anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S, intravenously at a dose of immunoglobulin 10% IgG solution (10% mL vial) for: Patient of 50 Kg or more, a dose of 50 mL, administered on days 1 and 3 of treatment. Patient under 50 Kg, the dose will be 1 mL / Kg, administered on days 1 and 3 of treatment. The supply of anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S included once it has been authorized by INVIMA and/or the regulatory requirements in force for the production of drugs are met.<br>|
| Active Comparator: Standard (specific) therapy<br>Standard therapy for COVID-19 according to the recommended pharmacological recommendations of the Colombian Association of Infectious Diseases - ACIN. This therapy is subject to changes that are defined by the Colombian Health Regulatory Authorities. To date, these therapies may include remdesivir, chloroquine, hydroxychloroquine, azithromycin. | Drug: Standard (specific) therapy for COVID-19<br>* Standard therapy for COVID-19 according to the recommended pharmacological recommendations of the Colombian Association of Infectious Diseases - ACIN. This therapy is subject to changes that are defined by the Colombian Health Regulatory Authorities. To date, these therapies may include remdesivir, chloroquine, hydroxychloroquine, azithromycin.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Admission to ICU and/or mechanical ventilation | Admission to the intensive care unit with the requirement of mechanical ventilation (invasive or non-invasive) due to Acute Respiratory Distress Syndrome by COVID-19. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Time in the hospital from admission to discharge or death. | One year | 
| Neutralizing antibody (IgG) titers against COVID-19 | Neutralizing antibody (IgG) titers against COVID-19 | One year | 
| Safety - Adverse events | Non-serious adverse events (NSAEs) and serious adverse events (SAEs) | One year | 
| Death | Overall mortality | One year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronavirus