. 2021 May 20;2021(5):CD013600. doi: 10.1002/14651858.CD013600.pub4

NCT04516811.

Study name	A prospective, randomized, placebo‐controlled, double‐blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID‐19
Methods	Trial design: randomised, double‐blinded, placebo‐controlled, phase III clinical trial Sample size: 600 Setting: inpatient Country: South Africa Language: English Number of centres: 1 Trial registration: NCT04516811 Date of registration: 18 August 2020
Participants	Inclusion criteria: Laboratory‐confirmed SARS‐CoV‐2 by positive RT‐PCR on any respiratory sample Age ≥ 18 years Require hospital admission for COVID‐19 pneumonia as defined by the presence of pulmonary infiltrates on chest X‐ray Moderate to severe COVID‐19 disease, defined as: SpO₂ ≤ 93% on room air; plus requiring non‐invasive oxygen therapy (WHO R&D BOSCI 4 or 5) Signed informed consent Pregnant women will be allowed to participate Exclusion criteria: Current participation in another therapeutic clinical trial for COVID‐19 Invasive mechanical ventilation Expected survival < 24 h based on clinical assessment (however, the study does not exclude critically ill patients who are not, due to resource limitations, candidates for critical care admission and/or mechanical ventilation) Known hypersensitivity to immunoglobulin or any components of the formulation
Interventions	Intervention(s): standard care and CP therapy Details of CP: Type of plasma: CP Volume: 200‐250 mL Number of doses: 1 Antibody test and antibody‐titre: NR Pathogen inactivated or not: NR RT‐PCR tested: NR Details of donors: Gender: NR HLA and HNA antibody: NR Severity of disease: NR Timing from recovery from disease: NR Treatment details, including time of plasma therapy (e.g. early stage of disease): moderate or severe COVID‐19 Comparator: standard care and saline (200 mL) Concomitant therapy: NR Duration of follow‐up: NR Treatment cross‐overs: nil
Outcomes	Primary study outcome: Clinical Improvement (time frame: Day 28). Proportion of participants with successful treatment outcome, defined as clinical improvement (≥ 2 points on WHO R&D BOSCI 1) by Day 28 post‐randomisation Primary review outcomes reported All‐cause mortality at hospital discharge: reported Time to death: reported 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: reported Number of participants with SAEs: reported Improvement of clinical symptoms, assessed through need for respiratory support at up to 7 days; 8‐15 days; 16‐30 days: reported WHO ordinal scale: NR 30‐day and 90‐day mortality: NR Admission on the ICU: reported Length of stay on the ICU: reported Time to discharge from hospital: reported QoL: NR Virological response: reported Additional outcomes: Inflammatory markers (time frame: Day 28) Radiography (time frame: Day 28) Fever and hypoxia (time frame: Day 28) Participants with HIV infection and other comorbidities (time frame: Day 28) Timing of IP and efficacy outcome (time frame: Day 28) Neutralising Ab (time frame: Day 28) SARS‐CoV antibody titre (time frame: Day 28)
Starting date	3 September 2022
Contact information	Contact: Cynthia Nyoni, +27117619279 ext 9279, Cynthia.Nyoni@sanbs.org.za Contact: Mpumi Maxebengula, BCom, +27214066497 ext 6497, mpumi.maxebengula@uct.ac.za
Notes	Recruitment status: Recruiting Prospective completion date: Dezember 2021 Sponsor/funding: Karin vandenBerg, Dr, South African National Blood Service