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

This study (n=464 adults) found the use of convalescent plasma was not associated with a reduction in progression to severe Covid-19 (PaO2/FiO2 <100 mm Hg) or all-cause mortality at 28 days post-enrolment (19% v 18% with standard care; risk ratio 1.04, 95% CI 0.71 to 1.54).

SPS commentary:

An accompanying editorial notes that the primary hypothesised mechanism of action of convalescent plasma is through direct antiviral action of neutralizing antibodies on SARS-CoV-2 RNA. The researchers observed a higher rate of conversion to a negative result for SARS-CoV-2 RNA on day 7 among patients in the intervention arm, however there was no net clinical benefit to patients. They discuss the prothrombotic effect of plasma and the recognition of Covid-19 as a thrombotic disorder. Although a review of the safety of convalescent plasma in the US (where it is available under an expanded access treatment protocol) found most of the 677 reported cardiac events (88.2%) and 113 thrombotic events (66.3%) were judged not to be related to transfusion, and were therefore excluded from the reported adverse event rates, adjudication of the “relatedness” of these events was conducted by the treating physician, with no defined protocol and no independent review.

It is recommended that:

  • the potential harms (especially prothrombotic risks) of the non-immune components of convalescent plasma be rigorously investigated
  • only donor plasma with detectable titers of neutralizing antibodies be given to trial participants
  • double blind designs with sham procedure controls should be the gold standard for future trials
  • non-immune plasma should not be used as a control intervention, because of potential harms and availability of lower risk alternatives such as normal saline.

British Medical Journal

Resource links:

Editorial