EUCTR2020‐001310‐38.

Study name	A randomized, prospective, open label clinical trial on the use of convalescent plasma compared to best supportive care in patients with severe COVID‐19
Methods	Trial design: open‐label, RCT Sample size: 120 Setting: inpatient Country: Germany Language: English Number of centres: 5
Participants	Inclusion criteria Patients with SARS‐CoV‐2 infection Age ≥ 18 years and ≤ 75 years SARS‐CoV‐2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swab) Severe disease defined by at least 1 of the following: respiratory rate ≥ 30 breaths/minute under ambient air requirement of any type of ventilation support needs ICU treatment   Written informed consent by patient or legally authorised representative Exclusion criteria Accompanying diseases other than COVID‐19 with an expected survival time of < 12 months In the opinion of the clinical team, progression to death is imminent and inevitable within the next 48 h, irrespective of the provision of treatment Interval > 72 h since start of ventilation support Not considered eligible for extracorporeal oxygenation support (even in case of severe ARDS according to Berlin classification with Horovitz‐Index < 100 mg Hg) Chronic obstructive lung disease (COPD), stage 4 Lung fibrosis with UIP pattern in CT and severe emphysema Chronic heart failure NYHA ≥ 3 and/or pre‐existing reduction of left ventricular ejection fraction to ≤ 30% Cardiovascular failure requiring ≥ 0.5 µg/kg/min noradrenaline (or equivalent) or requiring > 2 types of vasopressor medication Liver cirrhosis Child C Liver failure: bilirubin > 5 x ULN and elevation of ALT or AST (> 10 x ULN) Any history of adverse reactions to plasma proteins Known deficiency of IgA Pregnancy Breastfeeding women Volume overload until sufficiently treated Pulmonary oedema Participation in another clinical trial for treatment of COVID‐19
Interventions	Interventions CP therapy or hyperimmune immunoglobulin therapy: CP  Details of CP: type of plasma: fresh frozen plasma with marketing authorisation in Germany issued by Paul‐Ehrlich‐Institut  volume: NR number of doses: NR antibody‐titre: NR pathogen inactivated or not: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): within 72 hours of start of ventilation support For studies including a control group: comparator (type): randomised 1:1 to CP and best supportive care Concomitant therapy: NR Treatment cross‐overs: cross‐over allowed for patients with progressive COVID‐19
Outcomes	Primary study outcome: composite endpoint of survival no longer fulfilling criteria of severe COVID‐19 within 21 days after randomisation Primary review outcomes All‐cause mortality at hospital discharge: yes  Survival Time to death: yes Secondary review outcomes 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: case fatality rate at 21, 35, 60 days Admission on the ICU: NR Length of stay on the ICU: yes Time to discharge from hospital: yes QoL: NR Additional outcomes Time to clinical improvement on WHO R&D Blueprint seven‐category ordinal scale by 2 Time until negative SARS‐CoV‐2 PCR Predictive value of comorbidities and inflammation markers Feasibility of collection of plasma units Kinetics of anti‐SARS‐CoV‐2 antibodies in plasma of participants = plasma donors who recovered from a SARS‐CoV‐2 infection Titre of anti‐SARS‐CoV‐2 in transfused plasma units Impact of donor characteristics on anti‐SARS‐CoV‐2 humoral response Course of anti‐SARS‐CoV‐2 titre in participants Effect of timing of plasma transfusions on outcome
Starting date	6 April 2020
Contact information	Sixten Körper, IKT Ulm, 89081 Ulm, Germany; s.koerper@blutspende.de
Notes	Recruitment status: ongoing Prospective completion date: NR Sponsor/funding: DRK‐Bluspendedienst Baden‐Württemberg ‐ Hessen gGmbH, Germany