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

• Convalescent Plasma with antibody against SARS-CoV-2. (Other): 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.
• Standard treatment for COVID-19 (Other): The patients will receive the standard treatment for COVID-19, according to guidelines for COVID-19 (retrovirals drugs, interferon-α / β, anti-Interleukin-6 monoclonal antibody, oxygen therapy, etc..)

Primary outcomes

• Adaptive COVID-19 Treatment Trial Scale (ACTT) Version II [Day 7]: The scale provides a measure of COVID-19 severity based on the patient's physical situation, whose design was based on a blueprint of the WHO in treating COVID-19. * 1= Death * 2= Hospitalized. on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) * 3= Hospitalized. on non-invasive ventilation or high flow oxygen devices * 4= Hospitalized. requiring supplemental oxygen * 5= Hospitalized. not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) * 6= Hospitalized. not requiring supplemental oxygen - no longer requiring ongoing medical care. * 7= Not hospitalized. limitation on activities and/or requiring home oxygen * 8= Not hospitalized. no limitations on activities.
• Adaptive COVID-19 Treatment Trial Scale (ACTT) Version II [Day 14]: The scale provides a measure of COVID-19 severity based on the patient's physical situation, whose design was based on a blueprint of the WHO in treating COVID-19. * 1= Death * 2= Hospitalized. on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) * 3= Hospitalized. on non-invasive ventilation or high flow oxygen devices * 4= Hospitalized. requiring supplemental oxygen * 5= Hospitalized. not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) * 6= Hospitalized. not requiring supplemental oxygen - no longer requiring ongoing medical care. * 7= Not hospitalized. limitation on activities and/or requiring home oxygen * 8= Not hospitalized. no limitations on activities.

Secondary outcomes

• Anti-SARS-CoV-2 S IgG Serum Titer [At inclusion, Day 21]: The levels of Anti-SARS-CoV-2 S IgG serum
• Time of Hospitalization [Day 21]: time that the patients have passed in the hospital.
• Time to Negativization of RT-PCR [Day 21]: total time elapsed until negative RT-PCR test
• Diastolic Blood Pressure [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]: the pressure of blood in the artery when the heart relaxes between beats.
• Systolic Blood Pressure [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]: The pressure of blood in the artery when the heart contracts. It is the high number in a blood pressure measurement.
• Temperature [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]
• Cardiac Frequency [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]: The number of heart contractions or beats per unit of time. The normal values in adults at rest range between 60 and 100 beats per minit.
• Respiratory Frequency [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]: Number of breaths the patient takes per minute.
• Oxygen Saturation [At inclusion, Day 1, Day 3, Day 7, Day 14, Day 21]: blood oxygen percentage. A healthy percentage of oxygen in the blood is between 95% and 100%.
• Hemoglobin [At inclusion, Day 3, Day 7, Day 14, Day 21]: hemoglobin levels in the blood
• Leucocytes [At inclusion, Day 3, Day 7, Day 14, Day 21]: Leucocyte count a patient's blood.
• Neutrophils [At inclusion, Day 3, Day 7, Day 14, Day 21]: Neutrophils count a patient's blood.
• Absolute Lymphocytes [At inclusion, Day 3, Day 7, Day 14, Day 21]: lymphocyte count a patient's blood.
• Activated Partial Thromboplastin Time [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the number of seconds it takes for a clot to form in a patient's blood.
• Fibrinogen Level [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the level of fibrinogen in the blood (mg / dl), as a measure of assessing the severity of the disease.
• Fragment D-dimer Assessment [At inclusion, Day 3, Day 7, Day 14]: Determination of the existence of the D-dimer fragment in blood as a measure of assessing the severity of the disease.
• Glomerular Filtration Rate Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: estimation of how much blood passes per minute through the glomerular filters of the kidneys (ml/min).
• Troponin I Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the levels of troponin I proteins in the blood (ng/mL), as a measure of assessing the severity of the disease.
• Procalcitonin Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the levels of procalcitonin in the blood (ng/L), as a measure of assessing the severity of the disease.
• C-reactive Protein Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the level of c-reactive protein in the blood (mg/dl), as a measure of a change in inflammation
• Lactate Dehydrogenase (LDH) Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the level of lactate dehydrogenase in the blood (U/L), as a measure of assessing the severity of the disease.
• Interleukin-6 Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of serum levels Interleukin-6 in pg/mL, as a measure of assessing the severity of the disease.
• Ferritin Blood Assessment [At inclusion, Day 3, Day 7, Day 14, Day 21]: measurement of the amount of ferritin (blood protein) in ng/ml in the blood, as a measure of assessing the severity of the disease.
• Percentage of Patients Requiring Admission to Intensive Care Units. [Day 21]: Percentage of patients requiring admission to intensive care units.
• Mortality Rate at 15 Days [Day 15]: number of dead participants through day 15
• Mortality Rate at 30 Days [Day 30]: number of dead participants through day 30

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• Adaptive COVID-19 Treatment Trial Scale (ACTT) Version II (Primary), Count of participants, Participants: Control Group 0; Intervention Group 0
• Adaptive COVID-19 Treatment Trial Scale (ACTT) Version II (Primary), Count of participants, Participants: Control Group 0; Intervention Group 0
• Anti-SARS-CoV-2 S IgG Serum Titer (Secondary), Mean, AU/ ml: Control Group 90.28 +/- 53.51; Intervention Group 98.16 +/- 39.89
• Time of Hospitalization (Secondary), Mean, days: Control Group 10.5 +/- 1.8; Intervention Group 8.9 +/- 0.9
• Time to Negativization of RT-PCR (Secondary), Mean, days: Control Group 14.6 +/- 2.1; Intervention Group 12.4 +/- 1.4
• Diastolic Blood Pressure (Secondary), Mean, mmHg: Control Group 79.62 +/- 3.17; Intervention Group 75.21 +/- 2.12
• Systolic Blood Pressure (Secondary), Mean, mmHg: Control Group 130.62 +/- 5.84; Intervention Group 121.11 +/- 3.25
• Temperature (Secondary), Mean, degrees Celsius: Control Group 36.79 +/- 0.26; Intervention Group 36.43 +/- 0.14
• Cardiac Frequency (Secondary), Mean, beats/minit: Control Group 83.37 +/- 4.05; Intervention Group 79.82 +/- 2.25
• Respiratory Frequency (Secondary), Mean, breath/minut: Control Group 20.06 +/- 1.27; Intervention Group 22.42 +/- 1.25
• Oxygen Saturation (Secondary), Mean, percentage of blood oxygen: Control Group 95.31 +/- 0.73; Intervention Group 95.4 +/- 0.42
• Hemoglobin (Secondary), Mean, g/dL: Control Group 13.38 +/- 0.31; Intervention Group 13.45 +/- 0.29
• Leucocytes (Secondary), Mean, cells x10^9/L: Control Group 7.81 +/- 0.87; Intervention Group 7.40 +/- 0.46
• Neutrophils (Secondary), Mean, cells x10^9/L: Control Group 6.11 +/- 0.86; Intervention Group 5.50 +/- 0.48
• Absolute Lymphocytes (Secondary), Mean, cells x10^9/L: Control Group 1.165 +/- 0.11; Intervention Group 1.44 +/- 0.15
• Activated Partial Thromboplastin Time (Secondary), Mean, seconds: Control Group 29.62 +/- 1.43; Intervention Group 30.62 +/- 0.70
• Fibrinogen Level (Secondary), Mean, mg/dL: Control Group 713.13 +/- 44.64; Intervention Group 732.36 +/- 32.57
• Fragment D-dimer Assessment (Secondary), Mean, ng/mL: Control Group 350.26 +/- 62.80; Intervention Group 294.11 +/- 36.63
• Glomerular Filtration Rate Assessment (Secondary), Mean, ml/min: Control Group 80.44 +/- 5.41; Intervention Group 93.65 +/- 3.31
• Troponin I Assessment (Secondary), Mean, ng/mL: Control Group 6.55 +/- 1.59; Intervention Group 5.45 +/- 0.65
• 8 more outcome measures not shown.

Adverse events

Time frame: 21 days

Other adverse events by term

• Results publication: Bargay-Lleonart J, Sarubbo F, Arrizabalaga M, Guerra JM, Borras J, El Haji K, Flexas M, Perales J, Fernandez-Baca V, Gallegos C, Cruz MR, Velasco S, Lopez V, Cruz A, Bautista-Gili A, Jimenez-Marco T, Girona-Llobera E, Vilaplana L, Calonge L, Tena J, Galan MP, Payeras A. Reinforcement of the Standard Therapy with Two Infusions of Convalescent Plasma for Patients with COVID-19: A Randomized Clinical Trial. J Clin Med. 2022 May 27;11(11):3039. doi: 10.3390/jcm11113039. PMID 35683427

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2020-09-03)