High-Titer CCP Did Not Reduce Risk of Disease Progression in High-Risk Outpatients

August 19, 2021

Administration of high-titer COVID-19 convalescent plasma (CCP) within one week of COVID-19 symptom onset did not reduce the risk of disease progression compared to placebo, according to findings from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) published this week in the New England Journal of Medicine

The study’s results also showed that receipt of CCP did not influence clinically important secondary outcomes, including the severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization and death from any cause. Investigators halted the trial in February 2021 due to lack of efficacy based on a planned interim analysis. 

The trial enrolled 511 patients from 48 emergency departments throughout the United States, of whom 257 received CCP and 254 received placebo. Each participant had at least one risk factor for progression to severe COVID-19, such as obesity, hypertension, diabetes, heart disease or chronic lung disease. Within 15 days of treatment, progression to severe disease occurred in 77 (30%) of patients in the CCP group and in 81 (31.9%) patients in the placebo group.

The researchers wrote that the lack of efficacy of CCP could have resulted from insufficient doses of plasma or titers of neutralizing antibodies, the timing of administration, the selection of patients or the presence of potentially harmful components in the CCP that was administered. While the results suggest that CCP does not appear to benefit this particular group, study co-author Nahed El Kassar, MD, PhD, noted that the findings answer an important clinical question and may help bring researchers a step closer to finding more effective treatments against COVID-19. 

The authors also discuss the possible reasons why their results differed from those found by in the Argentine trial led by Libster, which randomized high-risk elderly patients to receive CCP or placebo very early after COVID-19 symptom onset. Using a primary endpoint of severe respiratory disease, the Libster trial found that 13/80 (16%) patients in the CCP cohort developed severe respiratory disease versus 25/80 (31%) of patients who received placebo, giving a relative risk reduction of 48%. The authors of C3PO note that patients in the Libster trial were older (77.2 years versus 51.6 years of age) and the CCP was administered earlier (median time from symptom onset was 39.6 hours in Libster trial versus 4 days in C3PO), which may contribute to the different findings in the two trials.

In response to the findings, AABB’s Chief Medical Officer Claudia S. Cohn, MD, PhD, said that the C3PO trial provided important information about CCP’s relative efficacy in the outpatient setting. Since this is only the second trial with published data in non-hospitalized patients, Cohn noted, it is a very useful contribution to the field. “It is clear that additional studies are needed to further elucidate CCP’s role in non-hospitalized patients,” she said.