Covid19, Immuno-Deficiency, Old Age; Debility
Conditions
Keywords
SARS-CoV-2, Convalescent plasma
Brief summary
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
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.
Interventions
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.
Sponsors
University Hospital, Basel, Switzerland
Ospedale Regionale di Lugano
Hôpital Fribourgeois
University Hospital, Geneva
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
open-label non-controlled, non-randomised interventional study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Immunocompromised patients defined as 1. Solid organ transplant ≤1 year before inclusion or treated for acute or chronic rejection episode or 2. Allogeneic stem cell transplant recipients ≤2 years before inclusion or treated for acute GvHD ≥grade 2 or chronic moderate-severe GvHD or 3. Active solid or haematological oncological disease with curative perspectives or 4. HIV infection with CD4\<350 or 5. Hypogammaglobulinemia and other severe genetic immunological defect or 6. Auto-immune disease with biological immunosuppressive treatment\* or 7. 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) 2. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) | 7 days after plasma infusion |
| Proportion of death | 28 days after plasma infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with cleared nasopharyngeal viral load | 7 days after plasma infusion | Cleared viral load is defined as CT value ≥30 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) | 21 days after plasma infusion | — |
| Proportion of patients with cleared nasopharyngeal viral load | 21 days after plasma infusion | Will be evaluated if CT\< 30 at 14 days |
Countries
Switzerland
Contacts
Primary ContactDiem-Lan Vu Cantero, MD, PhD
Backup ContactNina Khanna, MD
Outcome results
None listed