According to a new NIH-funded study, early administration of COVID-19 convalescent plasma in high-risk outpatients did not prevent disease progression.
COVID-19 convalescent plasma administered to high-risk outpatients with COVID-19 within 1 week after the onset of symptoms did not prevent disease progression in a new study published in the current online issue of NEJM.
The findings come from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO), which was funded by the National Institutes of Health (NIH) and the US Department of Health and Human Services. The trial was launched in August 2020 but was stopped in February 2021 because of a lack of efficacy based on a planned interim analysis.
“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 contact principal investigator Clifton Callaway, MD, PhD, professor of emergency medicine, University of Pittsburgh, in an NIH press release. “That was surprising to us. As physicians, we wanted this to make a big difference in reducing severe illness and it did not.”
Last year, the US Food and Drug Administration issued an emergency use authorization for convalescent plasma for the treatment of COVID-19 in hospitalized patients.
The aim of C3PO was to determine if convalescent plasma containing high titers of neutralizing antibodies was also beneficial in persons recently infected with SARS-CoV-2, but who were not severely ill and could be treated as outpatients.
The randomized, controlled trial enrolled 511 patients who presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management between August 2020 and February 2021.
All patients were aged ≥50 years (median=54 years) and had one or more risk factors for severe disease progression, such as obesity, hypertension, cardiovascular disease, or diabetes mellitus. Participants were randomly assigned to receive either 1 unit of high-titer convalescent plasma (n=257) or placebo (n=254).
The primary outcome was disease progression within 15 days post-randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization, according to the study.
Results showed that disease progression occurred in 77 participants (30%) in the convalescent plasma group compared to 81 patients (31.9%) in the placebo group. The convalescent plasma intervention did not cause harm, researchers added.
“The results show that convalescent plasma does not appear to benefit this particular group,” said C3PO co-author Nahed El Kassar, MD, PhD, medical officer, Blood Epidemiology and Clinical Therapeutics, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), in the press release. “But the findings answer an important clinical question and may help bring researchers a step closer to finding more effective treatments against this devastating disease.”
The lack of efficacy of convalescent plasma could have resulted from insufficient doses of plasma or titers of neutralizing antibodies, the timing of plasma administration, the selection of patients, or potentially harmful components in the plasma that was administered, concluded authors.
Additional studies of convalescent plasma are ongoing or planned in different populations, including an NIH-funded trial using it to treat hospitalized adult patients with COVID-19 to determine if it can help them recover quicker.
“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, MPH, chief of the NHLBI’s Blood Epidemiology and Clinical Therapeutics branch and who is coordinating the trial, in the press release.
Reference: Korley FK, Durkalski-Mauldin, SD, Yeatts SD, et al. Early convalescent plasma for high-risk outpatients with COVID-19. N Engl J Med. Online ahead of print. DOI: 10.1056/NEJMoa2103784.