Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Abstract

Objective: To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India.

Design: Open label, parallel arm, phase II, multicentre, randomised controlled trial.

Setting: 39 public and private hospitals across India.

Participants: 464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO₂/FiO₂) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm).

Interventions: Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study.

Main outcome measure: Composite of progression to severe disease (PaO₂/FiO₂ <100 mm Hg) or all cause mortality at 28 days post-enrolment.

Results: Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval -0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54).

Conclusion: Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19.

Trial registration: Clinical Trial Registry of India CTRI/2020/04/024775.

Fig 1

Trial profile

Fig 2

Comparison of biomarkers between intervention (convalescent plasma therapy+best standard of care) and control (best standard of care) arms, by days post-enrolment. The dark line in the box represents the median and the upper and lower edges of the box represent the interquartile range. The upper and lower extreme of the whiskers represent the upper and lower range, respectively, excluding outliers

Fig 3

Comparison of neutralising antibody titres between intervention (convalescent plasma therapy and best standard of care and control (best standard of care) arms, by days 0, 3, and 7 post-enrolment