Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)

Agarwal, A.; Mukherjee, A.; Kumar, G.; Chatterjee, P.; Bhatnagar, T.; Malhotra, P.; Latha, B.; Bundas, S.; Kumar, V.; Dosi, R.; Khambholja, J. K.; de Souza, R.; Mesipogu, R. R.; Srivastava, S.; Dube, S.; Chaudhary, K.; S, S.; Mattuvar K, S. A.; Rajendran, V.; Sundararajaperumal, A.; Balamanikandan, P.; Maheswari, R. S. U.; Jayanthi, R.; Ragunanthanan, S.; Bhandari, S.; Singh, A.; Pal, A.; Handa, A.; Rankawat, G.; Kargirwar, K.; Regi, J.; Rathod, D.; Pathrose, E.; Bhutaka, N.; Patel, M. H.; Verma, R. J.; Malukani, K.; Patel, S.; Thakur, A.; Joshi, S.; Kulkarni, R.; Suthar, N. N.; Shah, N. M.

Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.