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 severeCovid-19 (PROTECT-Patient trial)

South Africa is in the midst of an expanding Covid-19 epidemic. Inpatient mortality of Covid-19 is approximately 25%, and those requiring invasive mechanical ventilation have an extremely poor prognosis. Only two drugs have shown some efficacy in severe Covid-19, one of which, dexamethasone, is available in South Africa. Despite improved outcomes compared to standard of care, the mortality of patients receiving corticosteroids in the Recovery trial remained high. It is therefore a priority to rapidly investigate the efficacy of other potential therapeutic options that are safe, accessible, and affordable. Covid-19 convalescent plasma (CCP) refers to plasma collected from donors who have recovered from Covid-19 and likely have produced neutralising antibodies to SARS-CoV-2. Small uncontrolled studies CCP in China and US have shown potential benefit. Evaluation in randomised controlled trials has been recommended before CCP can be considered as a routine treatment option. PROTECT-patient a randomised, double-blinded, placebo-controlled, phase III clinical trial to assess the safety and efficacy of CCP for hospitalised patients with moderate to severe Covid-19. Six hundred participants admitted to participating private and public hospitals across South Africa will be randomized 1: 1 to CCP or saline placebo control. The primary outcome is clinical improvement, defined as ≥ 2 points on WHO Covid-19 Ordinal Improvement Scale by Day 28 post-randomisation. This multi-centre trial is a partnership between the South African National Blood Service and the University of Cape Town. Start-up funds are requested to support rapid implementation to generate evidence that will impact on the South African epidemic.