NCT04345523.

Study name	Multi‐center, randomized clinical trial of convalescent plasma therapy versus standard of care for the treatment of COVID‐19 in hospitalized patients
Methods	Trial design: multicentre, randomised, clinical trial  Sample size: 278 Setting: hospital Country: Spain Language: English Number of centres: 9
Participants	Inclusion criteria Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible Male or female adult patient ≥ 18 years of age at time of enrolment Laboratory‐confirmed SARS‐CoV‐2 infection as determined by PCR in naso/oropharyngeal swabs or any other relevant specimen Patients requiring hospitalisation for COVID‐19 without mechanical ventilation (invasive or non‐invasive) or high‐flow oxygen devices and at least 1 of the following: radiographic evidence of pulmonary infiltrates by imaging (chest X‐ray, CT scan, etc.), or clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air that requires supplemental oxygen Not > 12 days between the onset of symptoms (fever or cough) and treatment administration day Exclusion criteria Requiring mechanical ventilation (invasive or non‐invasive) or high‐flow oxygen devices > 12 days since symptoms (fever or cough) Participation in any other clinical trial of an experimental treatment for COVID‐19 In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 h, irrespective of the provision of treatments Any incompatibility or allergy to the administration of human plasma Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated GFR < 30)
Interventions	CP therapy or hyperimmune immunoglobulin therapy: CP  Details of CP: type of plasma: prepared approximately 140‐200 CP donors 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): early stage within 12 days  For studies including a control group: comparator (type): randomised 1:1 to CP and standard of care vs standard of care including any drugs that are being used in clinical practice (e.g. lopinavir/ritonavir; darunavir/cobicistat; hydroxy/chloroquine, tocilizumab, etc.), other than those used as part of another clinical trial Concomitant therapy: standard of care as specified above Treatment cross‐overs: none
Outcomes	Primary study outcome: category changes in ordinal scale (time frame: 15 days) (for categories: see additional outcomes) Primary review outcomes All‐cause mortality at hospital discharge: yes  mortality of any cause at 15 days (time frame: 15 days) mortality of any cause at 29 days (time frame: 29 days) Time to death: yes (up to 29 days) 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: NR (up to 29 days) Admission on the ICU: NR Length of stay on the ICU: NR Time to discharge from hospital: NR QoL: NR Additional review outcomes Category changes in ordinal scale (time frame: 15 days) proportion of patients in categories 5, 6 or 7 of the 7‐point ordinal scale at day 15 ordinal scale: not hospitalised, no limitations on activities not hospitalised, limitation on activities hospitalised, not requiring supplemental oxygen hospitalised, requiring supplemental oxygen hospitalised, on non‐invasive ventilation or high‐flow oxygen devices hospitalised, on invasive mechanical ventilation or ECMO death Time to category 5, 6 or 7 of the ordinal scale (time frame: 29 days) time to change from baseline category to worsening into 5, 6 or 7 categories of the ordinal scale Oxygenation‐free days (time frame: 29 days) Ventilator‐free days Change in biological parameters (time frame: days 1, 3, 5, 8, 11 and 29) ‐ serum levels of CRP, lymphocyte count, LDH, D Dimer, IL‐6, coagulation tests at baseline and days 3, 5, 8, 11, 15 and 29 Antibodies levels in CP donors recovered from COVID‐19 (time frame: 3 months) quantitative total antibodies and neutralising antibody activity against SARSCoV‐2 in the sera from donors and patients using viral pseudotypes Viral load (time frame: days 1, 3, 5, 8, 11 and 29) change in PCR for SARS‐CoV‐2 in naso/oropharyngeal swabs and blood at baseline and on days 3, 5, 8, 11 (while hospitalised); and days 15 and 29 (if able to return to clinic or still hospitalised)
Starting date	3 April 2020
Contact information	Cristina Avendaño Solá, MD, PhD +34 91 191 64 79 cavendano@salud.madrid.org
Notes	Recruitment status: recruiting (1 site, the rest not yet recruiting) Prospective completion date: July 2020 Sponsor/funding: Cristina Avendaño Solá