It is the first in the world to give an answer on the effectiveness of the therapy.
The expectations generated around the effectiveness of the use of convalescent plasma for the treatment of Covid-19 remain unsupported by robust evidence. In this context of uncertainty, a study carried out in 12 public and private institutions in five Argentine provinces contributed to shed light by concluding that it did not produce benefits in patients with pneumonia with criteria of severity.
“I want to highlight the importance of this essay, since it is the first globally to finish his enrollment and it allows to give an answer to a question that today was not yet given. This question was very important, considering the wide use of convalescent plasma in this disease, without having had a clear demonstrated effect so far, at least in the population we study, “said Ventura Simonovich, head of the Clinical Pharmacology Section of the Italian Hospital and one of the study’s principal investigators, during a press conference in which details of the results that had been leaked yesterday.
The PLASM-AR clinical trial participated 334 adult patients (the average age was 62 years and two out of three were men) with a confirmed diagnosis of Covid-19 pneumonia with some criterion of severity (determined by the decrease in oxygen concentration and / or clinical characteristics that could be associated with a bad evolution). As an exclusive condition, none could enter as a volunteer if they were receiving mechanical ventilation and all had to be in neurological conditions of consent participation in the study.
Because it is a study randomized, double blind, compared to placebo -the type of trials that allows to prove effectiveness-, neither the patients nor the researchers knew to which group each participant had been assigned, whether it was plasma (222 patients) or placebo (111). The median entry into the study was eight days after the onset of symptoms. “All had access to the medication they needed and more than 90% of our patients received, among other things, dexamethasone,” Simonovich said. So far, corticosteroids – and in particular dexamethasone – are the only treatment that has shown efficacy in patients with severe Covid-19 pneumonia.
“We make sure that the plasma doses we use count for the majority (more than 95%), with a level of quite superior neutralizing antibodies to what is recommended by international organizations, “said Leandro Burgos, deputy chief of Transfusion Medicine at the Italian Hospital.
The transfusion medicine teams from the different participating establishments were in charge of masking the bags containing the plasma and the placebo (physiological solution), with the aim that the content could not be seen and the cecum was protected.
About 500 donors were needed to gather the amount of plasma needed for the more than 200 patients who received the intervention. In measuring the level of antibodies, they had the collaboration and inputs provided by the laboratory of Andrea Gamarnik, from the Leloir Institute Foundation and researcher at Conicet, who led the development of the COVIDAR test, used in the framework of the study.
The analysis was based on the clinical results (how each patient did) and the time to clinical improvement, parameters that were measured on the day of entry to the study and at 7, 14 and 30 days. “In none of these endpoints, both in clinical and in outcome times, was the convalescent plasma group better than placebo,” Simonovich said.
Mortality was 10% in both groups. Among the 90% who were discharged, at 30 days, “the vast majority had made a complete recovery,” he said. “The conclusion that we draw for this study, the first that can give an answer for this population – patients with pneumonia with severity criteria – is that convalescent plasma is equal to a placebo“insisted the researcher and, when he described the results as” conclusive “, he stressed that” there was no benefit in either of the two branches “, not even of little significance.
“These population results they do not conflict or conflict with individual experiences, that many people have been able to have. There are many people who have received plasma and recovered and that is very good. In any case, what this study indicates is that possibly those same people would have recovered in the same way even if they had not received the plasma, “explained Waldo Belloso, coordinator of the Sponsored Research area of the Research department of the Italian Hospital.
And he added that this work “does not close the doors of convalescent plasma for Covid-19, since we analyze a particular population, which is that of patients with pneumonia with severity criteria. There are interventions in earlier stages of the disease in which our study cannot provide that answer. “
It is expected that the results of another of the ongoing trials in the country, led by the Infant Foundation and the Military Hospital, which studies the administration of convalescent plasma in the first 72 hours from onset of symptoms in patients with coronavirus infection between 65 and 74 years of age who present at least one underlying disease.
Convalescent plasma therapy has been used for more than a century in different diseases. In our country, it was used with great success in Argentine Hemorrhagic Fever, a pathology in which it reduced mortality from 30% to 3%. However, this procedure – in which the antibodies generated by a recovered person are transferred to a patient through plasma – has shown be effective in some infections, but not all.
There is still no strong evidence that plasma works in coronavirus patients and, if so, what would be the best way to use it. In August, preliminary results from an observational study of more than 35,000 Covid-19 patients in the United States showed “signs of efficacy,” according to a study by researchers from the Mayo Clinic.
But these results were obtained from patients treated through expanded access programs -as there is also in Argentina- to therapy (and not in controlled trials against placebo), a methodology that cannot demonstrate that plasma and not other care received were the true reason for the improvement in the benefited patients.
“When you consider the challenge of conducting a clinical research trial with a therapeutic intervention, of course you want it to have the efficacy that you are looking for. Especially in these types of pandemic situations where we need so much good news”, Belloso said, but stressed that “in this type of context is where we most have to take the appropriate methodology to be able to carry out the answer to the questions we ask ourselves, because reality does not always accommodate our wishes“.