PLACID Trial - a tour de force!

Contributed by Dr Chintan Kaswala

Convalescent plasma (CP) is a passive immunization strategy which has been used on several occasions in the past century. The results of very few large studies are available for the use of CP in COVID-19. All except one uncontrolled study has shown no benefit in terms of mortality or disease progression.

Recently, the results of one open-label, parallel-arm, phase II, multicenter, randomized controlled trial (PLACID trial) have been published. The trial was conducted by ICMR in 39 tertiary care hospitals across 14 states of India. Convalescent Plasma therapy was compared with the best standard of care (BSC) in hospitalized, nonpregnant, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). The patients were randomized in 1:1 ratio to receive either two doses of 200 ml convalescent plasma 24 hours apart or best standard of care. Plasma donors were males or nulliparous females aged between 18-65 years who had either completely recovered from symptomatic SARS CoV-2 infection before at least 28 days or were tested negative for 2 consecutive RT PCR tests 14 days after the symptom relief. The CP arm and the BSC arm had 235 and 229 participants respectively. Primary outcome measured was the composite measure of progress to severe disease (PaO2/FiO2 ratio <100) any time within 28 days of enrolment or all-cause mortality at 28 days.

Median duration from symptom onset to enrollment was 8 days in both the groups. 80% and 86% participants in BSC arm and CP arm respectively had detectable antibody titers at baseline. At 28 days follow-up the primary outcome was met in 41(17.9%) participants in the BSC arm vs 44(18.72%) in the CP arm. Even when stratified according to the baseline antibody levels in the CP group, the difference was not statistically significant. Similar proportion of the patients had received remdesivir and steroids in both the groups; however slightly larger number of patients had received Tocilizumab in BSC arm than in CP arm (12.7% vs 7.2%). In this study even when the time to initiation of CP was comparatively shorter than the previous studies, it didn’t show any benefit over the Standard of care.

Overall, it appears that CP has a limited role in the management of patients with moderate COVID 19.