The final results of the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) demonstrate that COVID-19 convalescent plasma did not prevent disease progression in a high-risk group of outpatients with COVID-19, when administered within the first week of their symptoms, reported the National Institutes for Health.
The trial was stopped in February 2021 due to lack of efficacy based on a planned interim analysis. The formal conclusions from the trial, which was funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, and by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, appear in The New England Journal of Medicine.
“We were hoping that the use of COVID-19 convalescent plasma would achieve at least a 10% reduction in disease progression in this group, but instead the reduction we observed was less than 2%,” said Clifton Callaway, M.D., Ph.D., the contact principal investigator for the C3PO trial and professor of emergency medicine at the University of Pittsburgh. “That was surprising to us. As physicians, we wanted this to make a big difference in reducing severe illness and it did not.”
COVID-19 convalescent plasma, also known as “survivor’s plasma,” is blood plasma derived from patients who have recovered from COVID-19. Last year, the U.S. Food and Drug Administration issued an Emergency Use Authorization to allow use of convalescent plasma in hospitalized patients with COVID-19. Researchers wanted to know whether administering COVID-19 convalescent plasma might also be beneficial in persons who were recently infected with SARS-CoV-2, the virus that causes the disease, but who were not severely ill and could be treated as outpatients. The objective was to prevent progression to severe COVID-19 illness.
The C3PO trial, launched in August 2020, was designed to answer that question.
The randomized, controlled clinical trial involved adult outpatients who presented to emergency departments with mild COVID-19 symptoms during their first week post-infection. The researchers randomly assigned the participants to receive treatment with either high-titer COVID-19 convalescent plasma (containing anti-COVID-19 antibodies) or placebo (salt solution infused with multivitamins and lacking antibodies).
Researchers compared outcomes in both groups within 15 days of treatment, looking specifically at whether the patients needed to seek further emergency or urgent care, were admitted to the hospital or died. The researchers found no significant difference in disease progression between the two groups. Of the 511 participants, disease progression occurred in 77 (30%) in the COVID-19 plasma group compared with 81 patients (31.9%) in the placebo group. The plasma intervention did not cause harm, the researchers found.
Additional studies of COVID-19 convalescent plasma are ongoing or planned in different populations.