Preemptive Use of Convalescent Plasma for High-risk Patients With COVID-19

Study Overview
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Brief Summary
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Convalescent plasma therapy has been recognized as safe and plasma transfusion is routinely used in clinical practice. A recent study showed that early administration of convalescent plasma can decrease the risk of complications in specific high-risk population. The aim of the present study is to offer convalescent plasma therapy to immunocompromised patients and older adults in the early phase of a SARS-Cov-2 infection in order to accelerate viral clearance and prevent complication

Detailed Description
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This is an open-label non-controlled, non-randomised interventional study. Study population consist in immunocompromised patients and older adults with or without co-morbidities. Included patients will receive at least one unit of convalescent plasma with NTAB titer ≥1:160 or equivalent at maximum 3-7 days after diagnosis by RT-PCR or symptom onset or if having mild-moderate disease (WHO scale <4). Patients will be followed-up up to 28 days to assess progression to WHO scale 4 disease, and 28-days mortality and viral load kinetics.

Official Title
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Preemptive Use of Convalescent Plasma for High-risk Patients With SARS-CoV-2 Infection: Phase III-IV Non-controlled Non-randomised Swiss Multicentric Trial

Conditions
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Immuno-Deficiency, Covid19, Old Age; Debility

Intervention / Treatment
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* Drug: SARS-CoV-2 convalescent plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunocompromised patients defined as Solid organ transplant ≤1 year before inclusion or treated for acute or chronic rejection episode or Allogeneic stem cell transplant recipients ≤2 years before inclusion or treated for acute GvHD ≥grade 2 or chronic moderate-severe GvHD or Active solid or haematological oncological disease with curative perspectives or HIV infection with CD4<350 or Hypogammaglobulinemia and other severe genetic immunological defect or Auto-immune disease with biological immunosuppressive treatment* or Other significant immunosuppressive condition such as IgG <6, treamtent with Rituximab or other biological lymphopenic treatment AND Age ≥ 18 years old and 2 distinct ABO group determination and Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 7 days and days post symptom onset (DPOS) ≤ 7 days at inclusion and/or No oxygen requirement (WHO 8 ordinal scale < 4): asymptomatic, mild or moderate disease, or O2 saturation ≥ 90% at room temperature and Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures) RT-PCR on a respiratory tract sample with CT value<20 or ascending kinetics at the time of infusion (highly suggested but not necessary) Older adults defined as Age ≥ 75 years old or ≥ 65 years old with at least one co-existing condition Arterial hypertension under pharmacological treatment Diabetes in treatment Obesity (BMI ≥ 30 kg/m2) Chronic obstructive pulmonary disease stade GOLD ≥2 Respiratory insufficiency due to any pneumopathy or neurologic disease. Cardiovascular disease as defined by either known coronary heart disease, history of ischemic or hemorrhagic stroke or cardiac insufficiency (ejection fraction <40%) Chronic kidney disease (GFR<60 ml/min) AND 2 distinct ABO group determination and Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 3 days and days post symptom onset (DPOS) ≤ 3 days at inclusion or RT-PCR on a respiratory tract sample with CT value<20 or ascending kinetics at the time of perfusion and No additional oxygen requirement compared to baseline (WHO 8 ordinal scale < 4): asymptomatic, mild or moderate disease and Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures) Exclusion criteria: Seroconversion at the time of inclusion Palliative care No signed informed consent History of previous transfusion-related Grade 3 adverse event according to Swissmedic definitions Disseminated intravascular coagulopathy (depending on specialist evaluation) Uncontrolled acute hypervolemia

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: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: open-label non-controlled, non-randomised interventional study
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: SARS-CoV-2 convalescent plasma|Included patients will receive at least one unit of convalescent plasma with NTAB titer ≥1:160 at maximum 3-7 days after diagnosis by RT-PCR or symptom onset. A second unit of plasma from a different donor can be proposed 24h after the first unit if immunocompromised and/or the patient received less than 3-5ml/kg of plasma volume. Additional units can be exceptionnally infused, at the investigator discretion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) |  | 7 days after plasma infusion | 
| Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) |  | 14 days after plasma infusion | 
| Proportion of death |  | 28 days after plasma infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with cleared nasopharyngeal viral load | Cleared viral load is defined as CT value ≥30 | 7 days after plasma infusion | 
| Proportion of patients with cleared nasopharyngeal viral load | Cleared viral load is defined as CT value ≥30 | 14 days after plasma infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Convalescent plasma