NCT04361253.

Study name	A prospective, randomized, double‐masked, placebo‐controlled trial of high‐titer COVID‐19 convalescent plasma (HT‐CCP) for the treatment of hospitalized patients with COVID‐19 of moderate severity
Methods	Trial design: phase 3 RCT, double‐blind (participant, investigator) parallel assignment Sample size: 110 in each arm (n = 220) Setting: e.g. inpatient Country: USA Language: English Number of centres: NR
Participants	Inclusion criteria Age > 1 year Active COVID‐19 infection confirmed by positive SARS‐CoV‐2 PCR Meets institutional criteria for admission to hospital for COVID‐19 Admitted to ICU or non‐ICU floor within 5 days of enrolment PaO2/FiO2 > 200 mmHg if intubated Patient or LAR able to provide informed consent Exclusion criteria: Previous treatment with convalescent plasma for COVID‐19 Current use of investigational antiviral therapy targeting SARS‐CoV‐2 History of anaphylactic transfusion reaction Clinical diagnosis of acute decompensated heart failure Objection to blood transfusion
Interventions	Intervention(s): e.g. COVID‐19 CP (HT‐CCP) Details of CP: Type of plasma: apheresis units Volume: 2 x 250 mL units (500 mL) Number of doses: 2 units administered sequentially over no greater than a 24‐h period Antibody‐titre: high; NR Pathogen inactivated: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): hospitalised patients but not yet in moderate or severe ARDS Comparator: e.g. conventional treatment 2 units of standard plasma (FFP)or FP24 (each 200‐275 mL, approximately 500 mL total) administered sequentially Concomitant therapy: NR Treatment cross‐overs: No
Outcomes	Primary study outcome(s): modified WHO Ordinal Scale score Primary review outcomes reported All‐cause mortality at hospital discharge: yes, using MOS up to 14 days Time to death: yes, up to 14 days Secondary review outcomes reported Number of participants with grade 3 and grade 4 adverse events, including potential relationship between intervention and adverse reaction (e.g. TRALI, transfusion‐transmitted infection, TACO, TAD, acute transfusion reactions): NR Number of participants with SAEs: NR Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8 ‐15 days; 16 to 30 days: yes, up to 14 days  30‐day and 90‐day mortality: NR Admission on ICU: yes  Length of stay on the ICU: yes up to 14 days Time to discharge from hospital: yes up to 14 days QoL: NR Additional outcomes Modified WHO Ordinal Scale score (time frame: day 14). The MOS numerical score is  0‐9 where a score of 0 attributes to 'no clinical evidence of infection' and a score of 9 attributes to 'death'. The eligibility requirements for this trial select individuals at level 3 or higher on the modified scale, but the day 14 outcome can be any one of 10 levels.
Starting date	30 April 2020
Contact information	Richard Kaufman, MD 617‐732‐5232 rmkaufman@bwh.harvard.edu Karina Oganezova 6177328624koganezova@bwh.harvard.edu Brigham and Women's Hospital, Boston, Massachusetts, USA, 02115
Notes	Recruitment status: recruiting Prospective completion date: December 2021 Sponsor/Funding: Brigham and Women's Hospital, Boston