NCT04364737.

Trial design: phase 2 RCT, double‐blind (participant, investigator) 1:1 ratio, parallel assignment

Sample size: 1000

Setting: inpatient

Country: USA

Language: English

Number of centres: 2

Inclusion criteria: 

• All sexes

• Patients ≥ 18 years of age

• Hospitalised for COVID‐19 respiratory symptoms

• Hospitalised for < 72 h or within day 3‐7 days from first signs of illness

• Laboratory‐confirmed COVID‐19

• On supplemental oxygen, non‐invasive ventilation or high‐flow oxygen

• Patients may be on other RCTs of pharmaceuticals for COVID ‐19 and patients who meet eligibility criteria will not be excluded on this basis

Exclusion criteria

• Receipt of pooled immunoglobulin in past 30 days

• Contraindication to transfusion or history of prior reactions to transfusion blood products

• Invasive mechanical ventilation or ECMO

• Volume overload secondary to congestive heart failure or renal failure

• Intracranial bleed

Intervention(s): SARS‐CoV‐2 donor CP

Details of CP:

• Type of plasma: NR (from New York Blood Center)

• Volume: ~250‐500 mL

• Number of doses: 1‐2 units

• Antibody‐titre: with antibodies to SARS‐CoV‐21 per 13 April 2020 directive by the FDA

• Pathogen inactivated: NR

Treatment details, including time of plasma therapy (e.g. early stage of disease): respiratory symptoms requiring oxygen supplementation within 3‐7 days from the onset of illness or within 3 days of hospitalisation

Comparator: e.g.. lactated Ringer's solution or sterile saline

• Equivalent volume to CP

Concomitant therapy: NR

Treatment cross‐overs: no

Primary study outcome(s):  

• Percentage of participants reporting each severity rating on WHO ordinal scale for clinical improvement (time frame: 14 days post randomisation)

  • No clinical or virological evidence of infection

  • 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

Primary review outcomes reported

• All‐cause mortality at hospital discharge: yes

  • see WHO Ordinal Scale up to 14 days post randomisation

• Time to death: yes

  • Mortality (time frame: 7, 14, 28 days post randomisation). Rate of mortality

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): no

• Number of participants with SAEs: no

• Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8 ‐15 days; 16 to 30 days: yes 

  • Percentage of subjects reporting each severity rating on WHO ordinal scale for clinical improvement (time frame: 14 days and 28 days post randomisation)

• 30‐day and 90‐day mortality: no

• Admission on ICU: yes

  • Rates of ICU admission (time frame: 7, 14, 28 days post randomisation). Percentage of patients requiring ICU admission.

• Length of stay on the ICU: no

• Time to discharge from hospital: no

• QoL: NR

Additional outcomes:

• Percentage of participants reporting each severity rating on WHO ordinal scale for clinical improvement (time frame: 28 days post‐randomisation). See above for criteria in scale

• Comparison in anti‐SARS‐CoV‐2 antibody titres (time frame: 0, 1, 7, 14, 28, 90 days post‐randomisation). Anti‐SARS‐CoV‐2 titres (IgM, IgG, IgA)

• Proportion positive in SARS‐CoV‐2 RNA (time frame: 0, 7, 14, 28 days post‐randomisation). SARS‐CoV‐2 PCR in nasopharyngeal swabs

• Changes from baseline in lymphocyte (time frame: 0, 1, 3, 7, 14 days post‐randomisation). Lymphocyte counts

• Changes from baseline in neutrophils (time frame: 0, 1, 3, 7, 14 days post‐randomisation). Neutrophil counts

• Changes from baseline in D‐dimer (time frame: 0, 1, 3, 7, 14 days post‐randomisation). D‐dimer level

• Changes from baseline in fibrinogen (time frame: 0, 1, 3, 7, 14 days post‐randomisation). Fibrinogen level

• Changes from baseline in T lymphocyte subsets (time frame: 0, 7, 28 days post‐randomisation). T cell subsets.

• Changes from baseline in B lymphocyte subsets (time frame: 0, 1, 3, 7, 14 days post‐randomisation). B cell subsets

Recruitment status: recruiting (NYU Langone Health​​​​​​​)

• Montefiore Medical Center Active‐ Not recruiting

Prospective completion date: 30 April 2023

Sponsor/Funding: NYU Langone Health; Albert Einstein Medical Center