NCT04408209.

Study name	Convalescent plasma for the treatment of patients with severe COVID‐19 infection ‐ a multicenter phase II trial
Methods	Trial design: interventional; historic control Sample size: 60 Setting: inpatient Country: Greece Language: English Number of centres: 6
Participants	Inclusion criteria Age > 18 years Confirmed SARS‐CoV2 infection by PCR of the nasal/pharyngeal swab, sputum, BAL Onset of the disease symptoms no more than 12 days before the inclusion of the patients in the trial Severe COVID‐19 infection as determined with one of the following: Respiratory rate 30/min Oxygen haemoglobin saturation SAT 93 CRP > 1.5 (ULN < 0.5) Ferritin value > 100 Ratio of PaO2:FiO2 < 300 mmHg Pulmonary infiltrates in chest X‐ray or chest CT scan > 50% during 24‐48 h Life‐threatening infection as determined by one of the following: Respiratory failure Septic shock Multiple organ failure Signature of informed consent by the patient or legal representative. Patients fulfilling criteria 1, 2, 3, 6 and one of criteria 4 or 5 will be eligible for the study. Exclusion criteria Critical illness due to progressive COVID‐19 with expected survival time < 48 h Intubated patients > 72 h Chronic heart failure NYHA 3 and/or pre‐existing left ventricular ejection fraction 30% Cardiovascular failure requiring 0.5 μg/Kg/min nor‐adrenaline or equivalent or > 2 types of vasopressor medication Liver cirrhosis Child C Liver failure with bilirubin > 5 x ULN and increase of ALT/AST (at least 1 > 10 x ULN) Previous history of allergic reaction to blood or blood products transfusion Known IgA deficiency Pregnancy Breast feeding women Pulmonary oedema Donor eligibility criteria All donors will be tested for: the titre of IgG anti‐SARS‐CoV‐2 antibodies (Pasteur Institute) the titre of neutralising anti‐SARS‐CoV‐2 antibodies (Pasteur Institute) Donor exclusion criteria NR
Interventions	Intervention(s): CP therapy Details of CP: Type of plasma: CP will be collected by plasmapheresis from patients fully recovered from COVID‐19 infection Volume: NR Number of doses: 3 Antibody‐titre: NR Pathogen inactivated NR Treatment details, including time of plasma therapy (e.g. early stage of disease): early treatment of patients with severe COVID‐19 Comparator: historical matched control Concomitant therapy: NR Treatment cross‐overs: not applicable
Outcomes	Primary study outcome: The primary endpoint of this trial is the survival on day 21. The primary endpoint, as a dichotomous composite of survival (yes/no) and no longer fulfilling criteria of severe COVID‐19, will be analysed according their classification. Survival (time frame: Day 21) Survival (time frame: Day 35) Survival (time frame: Day 60) Primary review outcomes reported All‐cause mortality at hospital discharge: yes Time to death: yes Secondary review outcomes reported Number of participants with grade 3 and grade 4 AEs, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions: yes Number of participants with SAEs: yes Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: yes 30‐day and 90‐day mortality: yes Admission on the ICU: NR Length of stay on the ICU: NR Time to discharge from hospital: NR QoL: NR Additional outcomes Clinical improvement, i.e. percentage of participants not fulfilling the criteria for severe disease (time frame: Day 21) The secondary endpoint of this trial is that no longer fulfilling criteria of severe COVID‐19 within 21 days after inclusion. This will be assessed on the basis of respiratory rate and ventilation support.
Starting date	23 April 2020
Contact information	Aikaterini Niarchou +30 6949124743 aniarchou@med.uoa.gr  Ioanna Charitaki +30 6976156403 j.charitaki@gmail.com
Notes	Recruitment status: recruiting Prospective completion date: 30 June 2020 Sponsor/funding: National and Kapodistrian University of Athens Hellenic Society of Hematology