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Inactivated Convalescent Plasma as a Therapeutic Alternative in Patients CoViD-19

Phase 2
Conditions
Infections, Coronavirus
Interventions
Drug: Inactivated convalescent plasma
Drug: Support treatment
Registration Number
NCT04385186
Lead Sponsor
National Blood Center Foundation, Hemolife
Brief Summary

Convalescent plasma is a way to provide passive immunity to a person exposed to an infectious agent. It has been used as a therapeutic tool for emerging viral infections without specific treatment and with high morbidity and mortality, such as Influenza H1N1, H5N1, H7N9, Ebola, MERS, SARS-CoV1, and even SARS-Cov2, with satisfactory results regarding evolution clinic of patients treated and without significant adverse events reported. One of its main advantages of convalescent plasma is to generate a rapid immune response (even faster than a vaccine), against a pathogen that circulates in a specific geographic area, probably common for both donor and recipient.

Detailed Description

This study consists of obtaining convalescent plasma by means of apheresis, from recovered donors, who meet the eligibility criteria to donate. Then this plasma will be inactivated by riboflavin and UV based photochemical treatment (Mirasol technology - Terumo BCT®), in order to add more transfusion security to the procedure. Finally, it will be transfused to CoViD-19 patients hospitalized in any of the participating clinics. There are currently no reported significant adverse events associated with this therapy. Have been published two serial cases reports,more evidence is necessary to standardize the treatment.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Over 18 years old
  • Confirmed laboratory diagnosis for qRT-PCR to SARS-CoV-2
  • Meet any of the following medical criteria (Defined by WHO): Be currently hospitalized with: Pneumonia, Severe pneumonia, Acute Respiratory Distress Syndrome (moderate or severe), Sepsis or Septic shock
  • The patient, or his representative, must sign an informed consent
Exclusion Criteria
  • Participate in another clinical trial for CoViD- 19
  • History of acute allergic transfusion reactions due to transfusion of blood or other components, especially plasma components (fresh frozen plasma, cryoprecipitate and platelets),
  • History of allergic reaction due to IgA deficiency
  • Allergic reaction to sodium citrate or riboflavin (vitamin B2)
  • History of immunosuppression

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Convalescent plasma+Support treatment selected by the hospitalInactivated convalescent plasmaParticipants will receive two doses of ABO - Rh compatible inactivated convalescent plasma, each one of 200 mililiters (mL), with a 24-hour interval via transfusion, for a final volume of 400 mL, meanwhile they continue to receive the supportive treatment chosen by the hospitals, according to each institutional protocol.
Convalescent plasma+Support treatment selected by the hospitalSupport treatmentParticipants will receive two doses of ABO - Rh compatible inactivated convalescent plasma, each one of 200 mililiters (mL), with a 24-hour interval via transfusion, for a final volume of 400 mL, meanwhile they continue to receive the supportive treatment chosen by the hospitals, according to each institutional protocol.
Support treatment selected by the hospitalSupport treatmentThe best support treatment selected by the hospital, according to each institutional protocol. Due to the ongoing development of knowledge of pathophysiology and scientific evidence of the available alternatives, it will be selected at the time of treatment.
Primary Outcome Measures
NameTimeMethod
Mortality reduction in CoViD-19 patients treated with inactivated convalescent plasma + support treatmentOver a period of 28 days

To assess the efficacy in reducing mortality in CoViD-19 patients treated with inactivated convalescent plasma together with the support treatment selected by the respective hospital

Secondary Outcome Measures
NameTimeMethod
Change in serum creatinine level3, 7, 14 and 28 days

Compare the change in Serum creatinine concentration at 3, 7, 14 and 28 days after treatment

Change in aspartate aminotransferase level3, 7, 14 and 28 days

Compare the change in aspartate aminotransferase level at 3, 7, 14 and 28 days after treatment

Radiography imagingOver a period of 60 days

Resolution of chest radiography imaging findings (example, bilateral, peripheral and basal predominant ground-glass opacity, consolidation, or both)

Antibody titerDay 0, Day 3 and Day 7

Neutralizing antibody anti SARS-CoV-2 titer evolution

Clinical evolutionOver a period of 28 days

Number of Participants with resolution of fever (\<38ºC temperature)

Change in lactate dehydrogenase level3, 7, 14 and 28 days

Compare the change in lactate dehydrogenase levels at 3, 7, 14 and 28 days after treatment

Viral Load0, 3, 7 days and until hospital discharge or a maximum of 60 days whichever comes first

Viral Load Quantification

Change in blood cell count3, 7, 14 and 28 days

Compare the change in blood cell count at 3, 7, 14 and 28 days after treatment

Change in bilirubin level3, 7, 14 and 28 days

Compare the change in bilirubin levels at 3, 7, 14 and 28 days after treatment

Change in creatine kinase MB level3, 7, 14 and 28 days

Compare the change in creatine kinase MB levels at 3, 7, 14 and 28 days after treatment

Change in C reactive protein concentration3, 7, 14 and 28 days

Compare the change in C reactive protein concentration at 3, 7, 14 and 28 days after treatment, in mg/L

Oxygen-free days through Day 60Until hospital discharge or a maximum of 60 days whichever comes first

Number of days without use of Oxygen

Mechanical ventilation-free days through Day 28Until hospital discharge or a maximum of 28 days whichever comes first

Number of days without use of mechanical ventilation

Clinical evolution by seven-parameter ordinal scale3, 7, 14 and 28 days

The clinical improvement will be established with a two-point improvement within this seven categories (recommended by World Organization Health-WHO): 1) Not hospitalized, with resumption of normal activities 2) Not hospitalized, but unable to resume normal activities 3) Hospitalized that does not require supplemental oxygen 4) Hospitalized requiring supplemental oxygen 5) Hospitalized requiring high-flow nasal oxygen therapy, non-invasive mechanical ventilation, or both 6) Hospitalized requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both 7) death

Multi-organ failure progression3, 7, 14 and 28 days

Evolution by SOFA (Sequential Organ Failure Assessment), The range is between 0 and 24 points, with the highest scores being indicators of a more serious illness

Change in alanin aminotransferase level3, 7, 14 and 28 days

Compare the change in Alanine aminotransferase levels at 3, 7, 14 and 28 days after treatment

Change in Procalcitonin concentration3, 7, 14 and 28 days

Compare the change in procalcitonin concentration at 3, 7, 14 and 28 days after treatment

Change in IL6 level3, 7, 14 and 28 days

Compare the change in IL6 level at 3, 7, 14 and 28 days after treatment

Assessment of oxygenation3, 7, 14 and 28 days

Arterial oxygen partial pressure (PaO2) in mmHg / Inspired fraction of oxygen (FIO2) ratio

Intensive Care Unit (ICU)-free days through Day 28Until hospital discharge or a maximum of 28 days whichever comes first

Time outside of ICU, in days

Change in hemoglobin concentration3, 7, 14 and 28 days

Compare the change in hemoglobin concentration at 3, 7, 14 and 28 days after treatment

Change in creatine kinase level3, 7, 14 and 28 days

Compare the change in creatine kinase levels at 3, 7, 14 and 28 days after treatment

Change in D Dimer concentration3, 7, 14 and 28 days

Compare the change in D Dimer concentration at 3, 7, 14 and 28 days after treatment

Tomography imagingOver a period of 60 days

Resolution of tomography imaging (example, patches located in the subpleural regions of the lung)

Hospital-free days through Day 60Until hospital discharge or a maximum of 60 days whichever comes first

Time outside of the hospital, in days

Trial Locations

Locations (10)

Clínica Antioquía

🇨🇴

Medellín, Antioquía, Colombia

Clínica Sagrado Corazón

🇨🇴

Medellín, Antioquía, Colombia

IPS Universitaria

🇨🇴

Medellín, Antioquía, Colombia

Universidad de Antioquía

🇨🇴

Medellín, Antioquía, Colombia

National Blood Center Foundation, Hemolife/Fundación Banco Nacional de Sangre Hemolife

🇨🇴

Bogotá, Cundinamarca, Colombia

Clínica Corpas

🇨🇴

Bogotá, Colombia

Clínica Rosales

🇨🇴

Pereira, Risaralda, Colombia

Clinica Nuestra

🇨🇴

Cali, Valle, Colombia

Clínica la Estancia

🇨🇴

Popayán, Colombia

E.S.E Hospital San Rafael Facatativa

🇨🇴

Facatativa, Colombia

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