The World Health Organization (WHO) began a large clinical trial on the action of drugs in the fight against Covid-19. The study, launched on March 20, is called Solidariedade (Solidarity) and will test four medicines on patients hospitalized due to the coronavirus. The initiative combines the efforts of scientists around the world. In Brazil, to date, 18 research centers are participating, including Unicamp. The first patient was included today (31/3), at the coordinating center in Rio de Janeiro (RJ).
The Solidariedade project, at the University, is coordinated by the infectious disease specialist and researcher at the Faculty of Medical Sciences (FCM), Mônica Jacques. The research team is based in the Department of Clinical Medicine at FCM, in the Discipline entitled Infectious Diseases. “Unicamp was invited to participate due to its experience with international multicenter clinical studies and previous experience of cooperative work with other Brazilian centers, not only in the context of clinical studies. The Diseases and Infectious Diseases discipline readily accepted the challenge, and with great enthusiasm, because we consider it a very relevant study.”
The professor, who works in the area of infectious diseases, explains that the study was created by the WHO to evaluate specific therapies for a Covid-19. “To date, there are some promising drugs, but with studies that are still preliminary, small, and lacking the power to document clinical outcomes. So the WHO chose to design what they are calling a mega trials, because it is a mega clinical study. It will be carried out with many patients to test four drugs that are the most promising and with evidence that they can inhibit the activity of the virus and have an impact on the evolution of the disease”.
The four medications are: chloroquine or hydroxychloroquine; remdesivir; the association lopinavir / ritonavir and, finally, the combination of lopinavir/ritonavir with Interferon Beta 1a. Some of these drugs, such as chloroquine and lopinavir/ritonavir, are approved for the treatment of other diseases, such as malaria, autoimmune diseases and HIV. Others have anti-viral action and have already been tested for Ebola and MERS. All have been evaluated as a potential treatment for COVID-19, a disease caused by the Sars-Cov-2 virus, the new coronavirus that affects humans and is the cause of the current pandemic.
Research
In each country involved in the study, there is a research center that coordinates the actions. In the case of Brazil, the National Institute of Infectious Diseases (INI) Evandro Chagas - Fiocruz, from Rio de Janeiro (RJ), is at the forefront. The data obtained will be systematized and analyzed by the WHO, which is also the supplier of the medicines.
The study follows patient inclusion and exclusion criteria, which primarily aim to protect participants. Furthermore, it is randomized. In this way, one of the four medications or just the standard treatment (without test drug) is chosen for the patient at random. The attending medical team, responsible for the treatment, does not decide which of the medications will be used, but is sovereign over all clinical decisions regarding the patient's treatment, and may even decide to interrupt the patient's participation in the study, if they consider that it is best for the patient. “There is no constraint on keeping the patient included in the study. This is the recommendation of the study protocol: the clinical decision is sovereign and the study procedures are secondary”, observes Mônica.
At Unicamp, the research will be conducted with patients admitted to the Hospital de Clínicas (HC) and will begin as soon as the medicines become available. The WHO is seeking to make shipping possible as quickly as possible. The study is easy to carry out, allowing the largest number of patients possible to be included. “The WHO designed a methodologically robust study, but at the same time simple to execute, which allows several centers around the world to contribute with the largest possible number of patients and which has the power, from a statistical point of view, to state which medicine is better”, highlights the teacher.
Further study
In Solidariedade, the central objective is to verify the relationship between the use of drugs and discharge or death rates. However, each research center will also be able to deepen studies and propose multi-center sub-studies, taking advantage of the huge research network surrounding Covid-19. Through a local initiative, it will be possible to research, for example, whether after discharge patients have pulmonary, psychiatric, hepatic or other sequelae. The study also opens the field for multicenter studies of pathogenesis, other clinical outcomes, and subpopulation analyses.
“Obviously, we researchers want to know what happens to these patients after discharge. We can propose studies of follow-up [patient monitoring] and epidemiological studies. Anyone who has a good research proposal, which obviously does not interfere with Solidariedade, can propose it to the group. Everyone's desire is to carry out as many multicenter studies as possible and provide information to improve care for these patients and perhaps to combat other epidemics”, assesses Mônica.
For the infectious disease specialist, multicenter research has the potential to produce an important volume of knowledge. “It is difficult to expand knowledge in the clinical area just in a research group. So we join forces, with the support and support of the WHO. I consider it an important, promising study with a great chance of bringing a lot of information and opening up space for researchers to work in cooperation at Unicamp.”
The professor also highlights that, as the name of the essay indicates, the relevance of the research lies in seeking solutions for humanity in the face of the pandemic, with benefits not only for those affected by Covid-19, but for the scientific community, strengthening ties of international cooperation.
