Use of convalescent plasma therapy in coronavirus-infected patients does not help in reducing mortality or progression to severe COVID-19, a multi-centric study funded by the Indian Council of Medical Research (ICMR) has found. The study has not yet been peer-reviewed and has now appeared on medRxiv, a preprint server.
The ‘open-label parallel-arm phase II multicentre randomized controlled trial’ (PLACID Trial) was conducted across 39 public and private hospitals across India between April 22 and July 14 to find effectiveness of convalescent plasma (CP) for the treatment of COVID-19, it said.
The National Task Force for COVID-19, a committee formed by the ICMR to respond to the pandemic, has reviewed and approved this study, it said.
The Clinical Management Protocols for COVID-19 issued by the Union Health Ministry on June 27 allowed use of convalescent plasma (Off label) for treating coronavirus-infected patients in moderate stage of the illness under “investigational therapies.”
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“The CP was not associated with reduction in mortality or progression to severe COVID-19,” the study said, adding this trial has high generalisability and approximates real-life setting of CP therapy in settings with limited laboratory capacity.
A prior measurement of neutralising antibody(NAb) titres in donors and participants may further clarify the role of CP in management of COVID-19, it said.
The study trial included 464 moderately ill coronavirus infected hospitalised patients, of whom 235 were given convalescent plasma along with best of standard care while 229 received only standard care, as per the study.
Plasma therapy is no silver bullet
Those in the intervention arm received two doses of 200 ml of CP, transfused 24 hours apart, in addition to the BSC (best standard of care). The two plasma units were collected preferably from different donors depending on the availability and ABO compatibility to increase chances of receiving CP with NAb, it said.
“The PLACID trial results indicate that there was no difference in 28-day mortality or progression to severe disease among moderately ill COVID-19 patients treated with CP along with BSC compared to BSC alone,” the study said.
The central implementation team at the ICMR was responsible for study design, study coordination, data analysis, data interpretation and writing of the report. Patient enrolment, data collection and actual conduct of the study was done at public and private hospitals independently and the investigators in the ICMR had no role in it.
Trial from China and Netherlands
According to the study, only two randomised controlled trials on CP use in COVID-19 have been published, one from China and the other from the Netherlands. Both were halted prematurely, the China study due to inadequate patient enrolment and the one from the Netherlands due to a need to redesign the trial based on interim findings.
In both studies, no mortality benefit was noted, and the Dutch study raised uncertainties regarding pre-transfusion antibody-status of patients as a potential factor in identifying appropriate candidates for CP therapy.
This uncertainty in the published evidence is reflected in a recent systematic review, which remained undecided on both the safety and effectiveness of CP as a therapeutic option in hospitalized patients of COVID-19.
“Given these uncertainties, we undertook the current study to determine the effectiveness of using CP in moderately ill COVID-19 patients admitted to hospitals across India in limiting progression to severe disease and determine the associated short-term adverse effects,” the study said.
All participants or their family members or legally authorised representatives were provided with information regarding the trial in a language they were comfortable with, and written informed consent was obtained prior to participant recruitment, it said.
