Clinical Trial to Evaluate the Efficacy of Treatment With Hyperimmune Plasma Obtained From Convalescent Antibodies of COVID-19 Infection

Study Overview
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Brief Summary
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Phase I / II multicentre, randomized and controlled clinical trial to evaluate the efficacy of treatment with hyperimmune plasma obtained from convalescent antibodies of COVID-19 infection.

Official Title
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Phase I / II Multicentre, Randomized and Controlled Clinical Trial to Evaluate the Efficacy of Treatment With Hyperimmune Plasma Obtained From Convalescent Antibodies of COVID-19 Infection

Conditions
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SARS-CoV 2

Intervention / Treatment
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* Biological: Hyperimmune plasma
* Drug: Standard of care for SARS-CoV-2 infection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent prior to performing procedures. the oral consent be accepted testified to prevent paper handling. Patient of both sexes, and ≥18 years. SARS-CoV-2 infection determined by PCR in a sample of naso-oropharyngeal exudate or other respiratory specimen or determination of specific positive IgM antibodies, in <72 hours before randomization. Patients requiring hospitalization for pneumonia COVID-19 without need until randomization of mechanical ventilation (invasive or non-invasive), and at least one of the following: O2 saturation ≤ 94% in ambient air, or PaO2 / FiO2 ≤ 300 mm Hg. Age> 65 years. Presence of: high blood pressure, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, or other chronic pulmonary and cardiovascular diseases, diabetes, or obesity Exclusion Criteria: Requirement before randomization of mechanical ventilation (invasive or non-invasive). Any of the following analytical data before randomization: IL-6> 80 pg / mL, D-dimer> 10 times ULN, ferritin> 1000ng / mL. Participation in another clinical trial or experimental treatment for COVID-19. In the opinion of the clinical team, progression to death or mechanical ventilation is highly probable within 24 hours, regardless of treatment provision. Incompatibility or allergy to the administration of human plasma. Severe chronic kidney disease grade 4 or requiring dialysis (ie eGFR <30) Pregnant, lactating, or fertile women who are not using an effective method of contraception. It is considered a woman of childbearing age all women from 18 years and up to a year after the last menstrual period in the case of menopausal women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br> | Biological: Hyperimmune plasma<br>* PLASMA OF CONVALESCENT COVID-19<br>|
| Active Comparator: Comparator<br> | Drug: Standard of care for SARS-CoV-2 infection<br>* Standard of care for SARS-CoV-2 infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of Adverse Events and Serious Adverse Events grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). | Incidence of Adverse Events and Serious Adverse Events grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). | 30 days after enrollment | 
| Efficacy: Death from any cause |  | Day +21 after randomization | 
| Efficacy: Need for mechanical ventilation |  | Day +21 after randomization | 
| Efficacy: Any of the following analytical data after 72h of randomization. | IL-6> 80 pg / mL, D-dimer> 10 times, ferritin> 1000 ng / mL. | Day +21 after randomization | 
| Efficacy: SOFA scale ≥ 3 after 72 hours of randomization or an increase of 2 points or more from the basal level |  | Day +21 after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy. Mortality on days 14 and 28. |  | Days 14 and 28. | 
| Efficacy: Proportion of patients who required mechanical ventilation |  | Until day 28 | 
| Efficacy: Proportion of patients who develop analytical alterations. | IL-6> 80 pg / mL, D-dimer> 10 times, ferritin> 1000 ng / mL until the cure test. | Day +21 after randomization. | 
| Efficacy: Cure / clinical improvement (disappearance or improvement of signs and symptoms of COVID-19) in the cure test. |  | Day +21 after randomization | 
| Efficacy: PCR negative for SARS-CoV-2 |  | On days 7 and 21 | 
| Efficacy: Proportion of patients requiring treatment. | Proportion of patients requiring treatment with Tocilizumab Sarilumab, Anakimra or other IL-6 or IL-1 antagonists, or corticosteroids at doses of methylprednisolone greater than 2 mg / Kg / day (or equivalent) and / or any investigational medication. | Until day 21. | 
| Efficacy: Duration of hospitalization (days) |  | Until day 21. | 
| Virology and immunological variables: Qualitative PCR for SARS-CoV-2 in naso-oropharyngeal exudate sample |  | At baseline and on day 21 | 
| Virology and immunological variables: Total antibody quantification |  | At baseline and on days 3, 7 and 21 | 
| Virology and immunological variables: Quantification of total antibodies in PC donors recovered from COVID-19. |  | Before infusion |