Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma

Study Overview
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Brief Summary
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The coronavirus disease 2019 (COVID-19) was classified as a pandemic by the WHO in March 2020. The SARS-COV-2 virus is easily transmissible and there is currently no approved treatment with effective results. Although the main epidemiological parameters are currently being studied, apparently the speed of contagion, the incidence and the mortality rate in severe cases appear to be high. Therefore, there is an urgent need to find a viable therapeutic option. The present trial is a pilot study with an objective to determine the efficacy of standard treatment reinforced with two repeated doses in two consecutive days of plasma from former convalescent people of the COVID-19 disease already discharged and / or with results in negative COVID-19 screenings, transfused to hospitalized COVID-19 patients.

Official Title
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Study of the Efficacy of Reinforcing of the Standard Therapy in COVID-19 Patients With Repeated Transfusion of Immune Plasma From COVID-19 Convalescents vs Exclusive Standard Therapy in Hospitalized COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Other: Convalescent Plasma with antibody against SARS-CoV-2.
* Other: Standard treatment for COVID-19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the HIP and sign the study IC male or female =/> 18 years Patient hospitalized with a COVID-19 diagnosis by PCR on nasopharyngeal swabs or any other biological sample. Presence of respiratory symptoms and / or fever associated with COVID-19, with clinical evolution time for COVID-19 equal to or less than 7 days. Presence of pneumonia on chest X-ray and / or SatO2 <94% aa. Sequential Organ Failure Assessment (SOFA) score ≤ 6. Accept the condition of complying with the procedures established in the protocol. Exclusion Criteria: Patients with a previous history of allergic transfusion reaction. Lactating or pregnant women and a positive pregnancy test. Patients who have been treated with plasma in the 21 days prior to the screening / baseline visit. Patients who are at the time of study, participating in another clinical trial. Patients who haven't completed all study procedures.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control group<br>Standard treatment for COVID-19 (according to clinical guidelines for COVID-19). | Other: Standard treatment for COVID-19<br>* The patients will receive the standard treatment for COVID-19, according to guidelines for COVID-19 (retrovirals drugs, interferon-α / β, anti-IL-6 monoclonal antibody, oxygen therapy, etc..)<br>|
| Experimental: Intervention group<br>Convalescent patient plasma 300 ml given in 2 consecutive days, plus standard treatment for COVID-19 (according to clinical guidelines). | Other: Convalescent Plasma with antibody against SARS-CoV-2.<br>* Convalescent plasma plus standard treatment for COVID-19. The convalescent plasma is from patients recovered from COVID-19 and negative viremia in the test detection COVID-19. The infusions will be given on days 1 and 2, of the study, after the positive result for COVID-19 of the recipient patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO clinical progression scale | The scale provides a measure of illness severity across a range from 0 (not infected) to 9 (Mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO) | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lung X-ray | Evaluation of the lungs with a chest x-ray | At inclusion, Day 21 | 
| Concomitant medication assessment | Indicate if the patient had to take a concomitant medication and specify the type of medication. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Hematimetry | blood count | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Activated partial thromboplastin time | measurement of the number of seconds it takes for a clot to form in a patient's blood. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Fibrinogen level | measurement of the level of fibrinogen in the blood (mg / dl), as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Fragment D-dimer assessment | Determination of the existence of the D-dimer fragment in blood as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Glomerular Filtration Rate assessment | estimation of how much blood passes per minute through the glomerular filters of the kidneys (ml/min). | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Ferritin blood assessment | measurement of the amount of ferritin (blood protein) in ng/ml in the blood, as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| C-reactive protein assessment | measurement of the level of c-reactive protein in the blood (mg/dl), as a measure of a change in inflammation | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Lactate Dehydrogenase (LDH) assessment | measurement of the level of lactate dehydrogenase in the blood (U/L), as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Troponin I assessment | measurement of the levels of troponin I proteins in the blood (ng/L), as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Procalcitonin assessment | measurement of the levels of procalcitonin in the blood (ng/ml), as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Interleukin-6 assessment | measurement of serum levels Interleukin-6 in pg/mL, as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| partial pressure of oxygen (pO2) assessment | measurement of the oxygen pressure in the blood (mmHg), as a measure of assessing the severity of the disease. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Quantitative determination of antibodies | Anti-SARS-Cov 2 immunoglobulin G / A level and anti-SARS-Cov 2 neutralizing antibody levels. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| SARS-Cov-2 viral quantification in a nasopharyngeal specimen | RT-PCR test for the diagnosis of SARS-COV-2 virus | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Time to negativization of RT-PCR | total time elapsed until negative RT-PCR test | Day 21 | 
| Pneumonia Severity Index (PSI) score | be used to assess the COVID-19 severity and predict the 14-day mortality risk in cases of COVID-19 pneumonia. The patient is then stratified into five classes ( class I: low risk, class V: high risk by his/her score on the PSI scale based on physical or laboratory examination. | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Percentage of patients requiring admission to intensive care units. |  | At inclusion, Day 3, Day 7, Day 14, Day 21 | 
| Mortality rate at 15 days |  | Day 15 | 
| Mortality rate at 30 days |  | Day 30 | 
| Length of stay |  | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, Immune Plasma