WASHINGTON - The final results of a clinical trial show convalescent plasma did not prevent disease progression in a high-risk group of outpatients with COVID-19, the National Institutes of Health announced Wednesday.
Last year, the U.S. Food and Drug Administration issued an Emergency Use Authorization for 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 trial was stopped earlier this year due to lack of efficacy based on analysis, but the study’s formal conclusions were published Aug. 18 in The New England Journal of Medicine.
A total of 511 patients were enrolled in the trial at 48 hospital emergency departments in 21 states. Of those, 257 patients were in the convalescent-plasma group and 254 were in the placebo group. The median age of the patients was 54 years, and the median symptom duration was four days.
Researchers found disease progression occurred in 77 patients (30%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group, suggesting only a 1.9% difference in the reduction in disease.
"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."
Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.
"The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression," the study authors wrote. "The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization."
The reason the intervention did not produce the expected results is unclear, but researchers are continuing to look at possible explanations, including insufficient plasma dose, timing of plasma administration, host-related factors or other aspects of the host tissue responses to the infection.
According to the NIH, COVID-19 convalescent plasma, also known as "survivor’s plasma," is blood plasma derived from patients who have recovered from COVID-19.
Researchers said convalescent plasma may still play a role if it is administered before the development of native antibodies. The treatment may also be efficacious in preventing symptomatic COVID-19 after exposure.
"The results show that convalescent plasma does not appear to benefit this particular group," said Dr. Nahed El Kassar, 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. "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 results of the study echo similar results from three other randomized, controlled trials involving hospitalized patients that showed no improvement in clinical outcome in those who received convalescent plasma.
Last year, scientists and medical experts had to push back against the claims about the efficacy of the treatment of convalescent plasma, when then-President Donald Trump announced the FDA’s approval to issue emergency use authorization.
Trump hailed the decision as a historic breakthrough even though the treatment’s value had not been established yet. FDA Commissioner Stephen Hahn echoed Trump, claiming that 35 more people out of 100 would survive the coronavirus if they were treated with the plasma.
Hahn then had to apologize for overstating the benefits of the Mayo Clinic's observations from a study in spring 2020.
"I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction," Hahn tweeted.
The Mayo Clinic’s study found the seven-day mortality rate was reduced in patients transfused with the plasma within three days of COVID-19 diagnosis compared with patients transfused four or more days after COVID-19 diagnosis. The use of convalescent plasma with higher antibody levels was associated with reduced seven-day and 30-day mortality.
However, the study was not intended to be a clinical trial to determine the efficacy of convalescent plasma. It was established by the FDA as a program to increase access to plasma to help severely ill patients at the height of the pandemic and to determine the safety of plasma transfusions.