The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”
Covid-19: Trial of experimental “covid cure” is among worst medical ethics violations in Brazil’s history, says regulator
BMJ 2021; 375 doi: https://doi.org/10.1136/bmj.n2819 (Published 17 November 2021) Cite this as: BMJ 2021;375:n2819
- Luke Taylor
Violations of medical ethics and human rights committed in a trial of an experimental drug touted by President Jair Bolsonaro as a cure for covid-19 were the worst in Brazil’s history, the country’s research regulator has said.1
The clinical trial of proxalutamide “disrespected almost the entire protocol” and may have contributed to the deaths of as many as 200 people, said the National Health Council (CNS), which oversees clinical research in Brazil.2 Some of those people were not adequately informed of the risks they were undertaking in the trial, and some did not know that they were taking part in one, it said.
Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS.2 The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”3
Proxalutamide is an anti-androgen that blocks the function of some male hormones. It is being tested by China’s Kintor Pharmaceuticals for prostate cancer, breast cancer, and other uses. It has not been approved for use in any country but was talked up by Bolsonaro as a treatment for covid-19. Shortly after recovering from covid-19 he asked why it had not been approved for use and promised to make it available to all of Brazil.45
To test proxalutamide’s possible use against covid-19, Cadegiani—an endocrinologist and clinical director for Applied Biology—oversaw its prescription to a man exhibiting severe covid-19 symptoms. The report, which stated that after 24 hours the patient showed “marked improvement of symptoms and markers of disease severity,” was published in BMJ Case Reports on 26 February 2021.6
In February 2021 Cadegiani oversaw the drug’s administration to 645 patients with covid-19 at nine hospitals in Brazil’s Amazonas region as it was hit with a severe wave of infections. All patients were admitted to hospital, but none required mechanical ventilation at the start of the study. Usual care included medicines such as enoxaparin, colchicine, methylprednisolone, dexamethasone, or antibiotic therapy as necessary,7 and some were given unproven treatments such as ivermectin.8 Altogether, 317 patients received proxalutamide and 328 a placebo.
The trial, which was reported on the preprint server medRxiv7 and not peer reviewed, found that the 14 day recovery rate was 81.4% with proxalutamide and 35.7% with placebo (recovery ratio 2.28 (95% confidence interval 1.95 to 2.66); P<0.001). At 28 days the all cause mortality rate was reported to be 11.0% with proxalutamide and 49.4% with placebo (hazard ratio 0.16 (0.11 to 0.24)).
Around 200 people died in the trial, mostly in the control group, although the CNS said that it had received different figures in different reports.
“The reported results would be a miracle—if they were true,” said Jesem Orellana, an epidemiologist who has closely followed the effects of the gamma variant of covid-19 on the Amazon region at Brazil’s leading public health institute, Fiocruz. “Everything about this trial is suspicious and anything but clinical and randomised.”
- Correction: We amended this story on 18 November 2021 to state that Flavio Cadegiani is clinical director for Applied Biology, not Kintor Pharmaceuticals.
- Correction: We further amended this story on 29 November 2021 to clarify that patients who were included in the study did not require mechanical ventilation at the start of the study. We also clarified that Brazil’s drug regulator has not suspended the import of proxalutamide for trials that are already under way and that proxalutamide is being studied in a number of countries for treatment in covid-19 patients, not just in Argentina as previously stated.
- Correction: We also amended this story on 10 December 2021 to replace the sentence “The report, which stated that the patient was relieved of all symptoms in three days, was published in BMJ Case Reports on 26 February 2021” to say, “The report, which stated that after 24 hours the patient showed ‘marked improvement of symptoms and markers of disease severity,’ was published in BMJ Case Reports on 26 February 2021.” We also amended the link in reference 7.
- Correction: On 6 January 2022 we removed a reference to a statement from Unesco’s Network of Bioethics after The BMJ’s editors decided that it was not appropriate to quote from a statement that has been retracted.