Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

Abstract

Abstract Background Convalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial. Methods This was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days. Results The CP group were a higher risk group with higher ferritin levels (p<0.05) though respiratory indices did not differ. The primary outcome measure – ventilation – was required in 6 controls and 4 patients on CP (risk ratio 0.67 95% CI 0.22 – 2.0, p=0.72); mean time on ventilation was 10.5 days in the control against 8.2 days in patients on CP (p=0.81). There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. Conclusion There were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.