NCT04373460.

Study name	Comparison of the efficacy and safety of human coronavirus immune plasma (HCIP) vs. control (SARS‐CoV‐2 non‐immune) plasma among outpatients with symptomatic COVID‐19
Methods	Trial design: phase 2, double‐blind, RCT Sample size: 1344 Setting: inpatient Country: USA Language: English Number of centres: 1
Participants	Inclusion criteria: ≥ 18 years of age Competent and capable to provide informed consent Positive RNA test for presence of SARS‐CoV‐2 in fluid collected by oropharyngeal or nasopharyngeal swab Experiencing any symptoms of COVID‐19 including but not limited to fever (T> 100.5º F), cough, or other COVID‐associated symptoms like anosmia ≤ 8 days since the first symptoms of COVID‐19 ≤ 8 days since first positive SARS‐CoV‐2 RNA test Able and willing to comply with protocol requirements listed in the informed consent Exclusion criteria: Hospitalised or expected to be hospitalised within 24 h of enrolment Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect participant safety and/or compliance History of prior reactions to transfusion blood products Inability to complete therapy with the study product within 24 h after enrolment Receiving any treatment drug for COVID‐19 within 14 days prior to screening evaluation (off‐label like hydroxychloroquine, compassionate use or study trial related)
Interventions	Intervention(s): SARS‐CoV‐2 CP Details of CP: Type of plasma: plasma obtained from volunteers who have recovered from SARS‐CoV‐2 infection Volume: ~200‐250 mL  Number of doses: 1 Antibody‐titre: titre ≥ 1:320 or current FDA standard titre Pathogen inactivated: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): NR Comparator: standard control plasma Concomitant therapy: NR Treatment cross‐overs: no
Outcomes	Primary study outcome: Cumulative incidence of hospitalisation or death prior to hospitalisation (time frame: Up to day 28) Cumulative incidence of treatment‐related SAEs (time frame: Up to day 28) Cumulative incidence of treatment‐related grade 3 or higher AEs (time frame: Up to day 90  Primary review outcomes reported All‐cause mortality: possibly (two measures: prior to hospitalisation (incidence), death in hospital (time to event), both measures are combined with other measures, see primary and additional study outcomes) Admission to hospital: yes Secondary review outcomes reported Development of severe clinical COVID‐19 symptoms, defined as WHO Clinical Progression Scale ≥ 6 (WHO 2020e): NR Time to symptom onset: NR Clinical status, assessed by need for respiratory support with standardised scales (e.g. WHO Clinical Progression Scale, WHO Ordinal Scale for Clinical Improvement) at up to 7 days, 8 to 15 days, 16 to 30 days: NR Mortality (time to event): yes (time to death in hospital only) 90‐day mortality: yes (two measures: death prior to hospitalisation, death in hospital) Length of hospital stay, for hospitalised patients: NR Admission to the intensive care unit (ICU): yes (time to event, combined endpoint, see additional study outcomes) Viral clearance, assessed with RT‐PCR test: yes QoL: NR 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 (Incidence of adverse plasma transfusion reactions: Cumulative incidence of treatment‐related SAEs (time frame: Up to day 28), Cumulative incidence of treatment‐related grade 3 or higher AEs (time frame: Up to day 90): yes Number of participants with SAEs: yes Additional study outcomes Change in serum SARS‐CoV‐2 antibody titres (time frame: Days 0, 14, 28 and 90) Time to SARS‐CoV‐2 PCR‐negativity (time frame: up to day 28) Change in level of SARS‐CoV‐2 RNA (time frame: Day 0‐Day 28) Change in oxygen saturation levels (time frame: Day 0‐Day 28) Rate of participant‐reported secondary infection of housemates (time frame: up to day 90) Time to ICU admission, invasive mechanical ventilation or death in hospital  (90 days) Time to resolution of COVID‐19 symptoms (time frame: up to day 90) Impact of CP on outcome as assessed by change in hospitalisation rate (time frame: Day 0‐Day 90) Impact of donor antibody titres on hospitalisation rate of CP recipients (time frame: Day 0‐Day 90) Impact of donor antibody titres on antibody levels of CP recipients (time frame: Day 0‐Day 90) Impact of donor antibody titres on viral positivity rates of CP recipients (time frame: Day 0‐Day 90)
Starting date	4 May 2020
Contact information	David J Sullivan, MD: 410‐502‐2522; dsulliv7@jhmi.edu David Sullivan, MD: 410‐502‐2522; dsulliv7@jhmi.edu
Notes	Recruitment status: Recruiting Prospective completion date: 21 December 2022  Sponsor/funding: Johns Hopkins University, State of Maryland, Bloomberg Foundation, Principal Investigator: David J Sullivan, MD The Johns Hopkins University