Researchers in Argentina have found that neither clinical status nor overall mortality was improved in COVID-19 patients with severe pneumonia treated with convalescent plasma in a randomised trial, writes Molly Walker for MedPage Today. The study was published in The New England Journal of Medicine.
At 30 days in the 333-patient trial, the convalescent plasma group and the placebo group showed no significant difference in distribution of clinical outcomes on a 6-point ordinal scale ranging from recovery to death (OR 0.83, 95% CI 0.52-1.35, P=0.46), reported Dr Ventura Simonovich of Hospital Italiano de Buenos Aires, and colleagues.
Odds ratios less than one in this analysis reflect poorer outcomes with convalescent plasma versus placebo. Moreover, there was no significant difference between group mortality rates (10.96% with plasma versus 11.43% for placebo).
The FDA authorised convalescent plasma in August to treat patients hospitalised with COVID-19 on the basis of observational data, says , MedPage Today.
Since then, guideline authors have been wary of the treatment: the National Institutes of Health called then-current data “insufficient” to recommend for or against its use given a lack of "well-controlled, adequately powered, randomised clinical trials".
The Infectious Diseases Society of America (IDSA) recommended limiting use of convalescent plasma for COVID-19 patients to within the context of a clinical trial.
The IDSA noted that only one randomised trial had been completed at that time, showing no benefit. Two other randomised trials came to opposite conclusions, one indicating a benefit while the other found none; both were stopped early.
The PlasmAr study
The MedPage Today story continues: The current study, PlasmAr, was a multi-center double-blind, placebo-controlled trial at 12 sites in Argentina, where participants were assigned 2:1 to receive convalescent plasma or placebo.
Hospitalised adults were eligible if they tested positive for SARS-CoV-2, had radiologically confirmed pneumonia and no previous directives rejecting advanced life support, and at least one of the criteria for severity, such as oxygen saturation below 93%. Data were collected May 28-August 27.
Primary outcome was clinical status 30 days after intervention, as measured by an adapted version of the World Health Organization (WHO) clinical scale, ranging from 1 (death) to 6 (discharged with full return to baseline physical function).
Overall, 228 patients were randomised to receive convalescent plasma, while 105 were randomised to placebo. Median age of patients was 62, about 68% of patients were men and 65% had a pre-existing condition at trial entry.
In addition to no between-group differences in clinical status at day 30, there was no difference in clinical status on day 7 or day 14, according to MedPage Today.
Median time of onset of COVID-19 symptoms to enrolment was 8 days. More than 90% of patients were receiving oxygen and glucocorticoids at trial entry.
Examining safety, infusion-related adverse events were more common with plasma than placebo (4.8% vs 1.9%, respectively), and five patients in the plasma group had nonhemolytic febrile reactions. However, there was no significant between group difference in incidence of adverse events or severe adverse events.
"Our trial ensured that more than 95% of the transfused plasma units had a total anti-SARS-CoV-2 antibody titer of at least 1:800," the authors wrote.
Limitations to the data include that all enrolled patients had severe COVID-19 pneumonia, so conclusions cannot be extrapolated to mild and moderate cases, MedPage Today continues.
They also noted it was difficult to differentiate post-infusion reactions, including transfusion-associated cardiac overload and transfusion-related acute lung injury, from COVID-19 progression.
A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia
New England Journal of Medicine. Published on 24 November 2020
Authors
Ventura A Simonovich, Leandro D Burgos Pratx, Paula Scibona, María V Beruto, Marcelo G Vallone, Carolina Vázquez, Nadia Savoy, Diego H Giunta, Lucía G Pérez, Marisa del L Sánchez, Andrea Vanesa Gamarnik and Diego S Ojeda et al for the PlasmAr Study Group
Abstract
Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomised, controlled trials.
Methods
We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2B1 ratio to receive convalescent plasma or placebo. The primary outcome was the patientʼs clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death.
Results
A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrolment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrolment.
The infused convalescent plasma had a median titer of 1B3200 of total SARSCoV-2 antibodies (interquartile range, 1B800 to 1B3200].
No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46).
Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups.
Conclusions
No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo.
[link url="https://www.medpagetoday.com/infectiousdisease/covid19/89878"]MedPage Today story – Convalescent Plasma Flops for Severe COVID-19[/link]
[link url="https://www.nejm.org/doi/full/10.1056/NEJMoa2031304?query=TOC"]New England Journal of Medicinearticle – A Randomized Trial of Convalescent Plasma in COVID-19 Severe Pneumonia[/link]