Effectiveness and Safety of Convalescent Plasma in Patients With High-risk COVID-19

Study Overview
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Brief Summary
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global population with significant morbidity and mortality. One of the main concerns is the management of the patients since there is no specific treatment for this condition. Therefore, in SARS-CoV-2 patients the compassionate use of off-label therapies has been initiated; such as the use of plasma from convalescent patients. This treatment has been used in other pandemics like SARS-CoV-1, H5N1, H1N1, Ebola, among others. This study is a phase II/III randomized clinical trial to assess the effectiveness and safety of convalescent plasma administration in patients with high-risk SARS-CoV-2.

Detailed Description
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This is a Phase II/III randomized clinical trial to assess the effectiveness and safety of anti-SARS-CoV-2 convalescent plasma in i) hospitalized adult patients with high-risk of progression SARS-CoV-2 infection and ii) patients in Intensive Care Unit (ICU). Compatible ABO plasma from convalescent patients will be administered at a dose of 400 ml divided into two doses intravenously. Outcomes will be measured as follows: * Group of patients with critical illness: Primary outcomes (Effectiveness and safety): Mortality Safety: Presence of adverse events Secondary outcomes: Intensive care unit length of stay Evolution of clinical and paraclinical aspects. Group of patients at high risk of progression: Primary outcomes (Effectiveness and safety): Mortality Safety: Presence of adverse events Admission to ICU in 30 days Mechanical ventilation requirement Secondary outcomes: Hospital/Intensive care unit length of stay Evolution of clinical and paraclinical aspects.

Official Title
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Effectiveness and Safety of Convalescent Plasma in Patients With High-risk COVID-19: A Randomized, Controlled Study CRI-CP (Coronavirus Investigation - Convalescent Plasma)

Conditions
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Sars-CoV2, Covid-19

Intervention / Treatment
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* Biological: SARS-CoV-2 convalescent plasma treatment
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients Patients diagnosed with COVID-19 infection by RT-PCR technique Patients ≥ 18 years of age Patients in standard care according to the national guide Onset of symptoms ≤ 14 days Signature of informed consent report Patients at high risk of progression, defined by all of the following: Score greater than 9 on the CALL scale Pao2 / Fio2 ≤ 200 (parameters adjusted to the height of Bogotá, Colombia) X-ray or CT compatible with pneumonia Hospitalized patients Critically ill patients, defined by any of the following: Mechanical ventilation requeriment Patients in Intensive Care Unit or Intermediate Care Unit Ventilatory failure, septic shock, dysfunction or multi-organ failure Exclusion Criteria: Negative RT-PCR result from secretion 48 hours prior to study recruitment History of allergic reaction to blood or plasma in patients with a known history of IgA deficiency Patients participating in other clinical trial History of allergy to blood products History of confirmed infection and that required antibiotic or antifungal treatment 30 days prior to recruitment Pregnant women

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard care alone<br> | Other: Standard care<br>* Standard care according to guidelines and national regulations<br>|
| Experimental: SARS-CoV-2 convalescent plasma treatment plus standard care<br> | Biological: SARS-CoV-2 convalescent plasma treatment<br>* Plasma transfusion of convalescent patients from COVID-19 with negative RT-PCR, and antibody titers of 1:160 or greater at a dose of 400ml distributed in two doses administered on the same day intravenous administration<br>Other: Standard care<br>* Standard care according to guidelines and national regulations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Death of the patient (yes/no) | Up to 30 days after the study enrollment | 
| Adverse events | Presence of any of the following adverse events (yes/no): Nonhemolytic febrile reactions Allergic reactions Acute hemolytic reactions Non-immune hemolysis Acute transfusion-related lung damage Transfusion-related circulatory overload Metabolic reactions Hypotensive reactions Delayed hemolytic reactions Post transfusion purple Graft versus host disease Bacterial contamination of blood components Viral infections Other infections (syphilis, prions, malaria, Chagas, yellow fever, dengue) | Up to 30 days after the study enrollment | 
| ICU admission | Admitted to intensive care units (ICUs) (yes/no) | Up to 30 days after the study enrollment | 
| Mechanical ventilation | Mechanical ventilation requirement (yes/no) | Up to 30 days after the study enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU length | Intensive care unit length of stay | Up to 30 days after the study enrollment | 
| Reduction of D Dimer | D dimer reduction below 1mcg / ml | Assessment at day 30 after study enrollment | 
| LDH reduction | Reduction of LDH below 350 IU / L | Assessment at day 30 after study enrollment | 
| Reduction of Troponin level | Reduction of troponin level to than 8 pg / mL | Assessment at day 30 after study enrollment | 
| Decrease in ferritin level | Decrease in ferritin level below 1025 mcg / L | Assessment at day 30 after study enrollment | 
| Decrease in procalcitonin level | Decrease in procalcitonin level below 0.1ng / ml | Assessment at day 30 after study enrollment | 
| Decrease in CRP | Decrease in CRP level bellow <8 mg / L | Assessment at day 30 after study enrollment | 
| Increase in lymphocyte count | Increase in lymphocyte count greater than 0.6 x 10-9 / L | Assessment at day 30 after study enrollment | 
| Increase in PaO2 / Fio2 | Increase in PaO2 / Fio2 greater than 200 | Assessment at day 30 after study enrollment | 
| Decrease in Sequential Organ failure assessment (SOFA ) score | Scale of 24 points, greater number indicates worst outcome | Assessment at day 30 after study enrollment | 
| Extracorporeal membrane oxygenation (ECMO) | Extracorporeal membrane oxygenation requirement (ECMO) | Assessment at day 30 after study enrollment | 
| Lung infiltration | Decrease in the percentage of lung infiltration | Assessment at day 30 after study enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 serotherapy, Mortality, Safety