Published in the JAMA Network Open, the initial results of the CloroCovid-19 trial show that patients with severe Covid-19 should not take high doses of chloroquine. The trial, whose goal is to assess the efficacy of two different dosages of the drug and has analised 81 patients with SARS (severe acute respiratory syndrome), is being led by more than 70 researchers, post-graduation students, and collaborators from renowned scientific institutions, such as the Dr. Heitor Vieira Dourado Tropical Medicine Foundation (FMT-HVD), the University of the State of Amazonas, the University of São Paulo, and Fiocruz. For the part of the trial that studied the higher dose, researchers applied the same dosage used as treatment in China.
“The results of the trial should be taken as a warning, as they offer more robust evidence for treatment protocols for Covid-19”, explains researcher Marcus Vinícius Lacerda, the main investigator of the trial, who works at Fiocruz Amazônia and at FMT-HVD. According to Lacerda, up to this moment it is not yet possible to state that chloroquine is effective as treatment for people infected with the new coronavirus.
The trial was structured as a phase II study, focusing on the analysis of different dosages and on patient safety, including only those with SARS and suspected Covid-19 (later confirmed by laboratory tests). The trial analysed 81 individuals hospitalized at Hospital Delphina Aziz, a reference for Covid-19 in the state of Amazonas. The scientists in charge of the trial also took into account other issues such as the fact that higher doses have higher antiviral activity, proven in laboratory conditions, and may therefore be able to inhibit the new coronavirus.
The patients that participated in the study were divided in two groups that received two different doses of chloroquine in their treatment: a high dose (600 mg twice a day, for ten days) and a lower one (450 mg twice a day on the first day, and once a day for four days afterwards). The patients were followed by the research team for 28 days after first taking the drug.
The initial conclusions of the trial showed that severe Covid-19 patients should not be given the dose recommended by the Chinese Treatment Consensus. Up to the moment the study was released, no other trial anywhere in the world had shown evidence on this kind of use, as no suitable safety assessments had been carried out, such as daily EKGs - which was done in Manaus, under the guidance of experienced cardiologists.
Ethics and transparency in the trial
The trial was approved by the National Committee in Ethics in Research (Conep), registered under the number CAAE 30504220.5.0000.0005. The committee is made up of specialist physicians from Brazil and abroad, who started following the results on a daily basis. An independent safety and follow-up committee was also formed.
As soon as the first deaths of patients on any of the two doses of chloroquine occurred, Conep immediately requested the data analysis: 11 people (of both groups) had died due to Covid-19, an average number that was similar to global figures. These individuals were mostly elderly people and had the same profile of severe patients all over the world. The trial also showed that patients on the higher doses tended to have more side effects. All CloroCovid-19 patients are informed of the goal of the trial before the trial itself, and sign informed consents (TCLE, in the Portuguese acronym) that also state they are aware they may or may not be given chloroquine.
The high dose was immediately suspended and all participants started taking the lower dose. Conep received official communication of this through Plataforma Brasil, and for additional transparency and international visibility, the first results were published on the fast track of MedRxiv, to ensure suitable transparency and international visibility for the results until the study was peer reviewed.
CloroCovid-19 is an ongoing trial that is being developed by a team who has been carrying out studies on malaria, HIV/Aids, tuberculosis and other emerging diseases for years, with worldwide recognition and participation in international agencies, including the World Health Organization (WHO). The study was finenced by the government of the State of Amazonas, by the Coordination for the Improvement of Higher Education Personnel (Capes) and by the Foundation of Research Support of the State of Amazonas (Fapeam).