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. The trial was stopped in February 2021 due to lack of efficacy based on a planned interim analysis, according to a statement by the National Institutes of Health (NIH).
The statement further mentioned that the formal conclusions from the trial appear in the current online issue of The New England Journal of Medicine.
“We were hoping that the use of COVID-19 convalescent plasma would achieve at least a 10 per cent reduction in disease progression in this group, but the reduction we observed was less than two per cent,” said Clifton Callaway, MD, PhD, the contact principal investigator for the C3PO trial, and Professor, Emergency Medicine, University of Pittsburgh.
Callaway further said, “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 US Food and Drug Administration (FDA) issued an Emergency Use Authorisation (EUA) to allow the use of convalescent plasma in hospitalised 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, but who were not severely ill and could be treated as outpatients. The objective was to prevent progression to severe COVID-19 illness, added the statement.
It also said that the C3PO trial, launched in August 2020, was designed to answer that question. The randomised and controlled clinical trial involved adult outpatients who presented to emergency departments with mild COVID-19 symptoms during their first week post-infection. The trial was conducted by the SIREN clinical trials network, and enrolled more than 500 participants from 48 emergency departments across the US. The participants were racially and ethnically diverse with a median age of 54 years, and slightly more than half were women. Participants also had at least one risk factor for progression to severe COVID-19, such as obesity, hypertension, diabetes, heart disease or chronic lung disease. 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 per cent) in the COVID-19 plasma group compared with 81 patients (31.9 per cent) in the placebo group. The plasma intervention did not cause harm, the researchers found, according to the statement.
“The results show that convalescent plasma does not appear to benefit this particular group,” said Nahed El Kassar, MD, PhD, one of the study’s co-authors and medical officer in the Blood Epidemiology and Clinical Therapeutics branch of the NHLBI’s Division of Blood Diseases and Resources.
Kassar added, “But the findings answer an important clinical question and may help bring researchers a step closer to finding more effective treatments against this disease.”
The reason the intervention did not produce the expected results is unclear, Callaway said. Researchers are continuing to look at possible explanations, including insufficient plasma dose, the timing of plasma administration, host-related factors, or other aspects of the host tissue responses to the infection, he added.
Additional studies of COVID-19 convalescent plasma are ongoing or planned in different populations. These included the Pass It On trial, a nation-wide, NIH-funded randomised clinical trial using convalescent plasma to treat hospitalised adult patients with COVID-19 infection to see if the treatment can help them recover faster. Other trials include one in outpatients who are recovering at home and one in individuals with high risk of exposure to COVID-19 to see if COVID-19 convalescent plasma can prevent infection, the statement further said.
“We need the results of these other convalescent plasma studies to get a clearer, more conclusive picture of its value for future treatments of COVID-19,” said Simone Glynn, MD, MP and Chief, Blood Epidemiology and Clinical Therapeutics, NHLB, who is coordinating the trial.