South Africa is preparing to start two clinical trials involving the much-debated drugs hydroxychloroquine and chloroquine, which is being discussed for its effectiveness to treat Covid-19.
In May, President Donald Trump said he had been taking hydroxychloroquine as a preventive measure against Covid-19. His advised remarks prompted the Food and Drug Administration to issue warnings against taking hydroxychloroquine for anything other than malaria and some auto-immune conditions, like lupus.
Currently, there are different trials examining the effectiveness of hydroxychloroquine and chloroquine. One of them, the Solidarity Trial, launched by the World Health Organization (WHO), compares four drugs with the aim of assessing their effectiveness in treating Covid-19. Hydroxychloroquine is one of them.
Infectious diseases specialist from the University of the Witwatersrand Jeremy Nel, said the Solidarity Trial’s independent data and safety monitoring committee has reviewed evidence from this and other trials, and concluded that hydroxychloroquine presents no evidence of harm.
Chloroquine and hydroxychloroquine were developed originally to treat and prevent malaria. Hydroxychloroquine is now mostly used in South Africa to reduce pain and swelling in rheumatoid arthritis.
An influential study
Recently, there have been debates whether hydroxychloroquine or chloroquine increases the risk of death in patients with Covid-19. This came after The Lancet, the pre-eminent weekly medical journal, published a study on 22 May 2020 that flagged danger in using chloroquine and hydroxychloroquine to treat Covid-19. It looked at 96 032 Covid-19 patients in 671 hospitals across the world.
The study divided patients into groups: 3 016 received hydroxychloroquine, while 6 221 received hydroxychloroquine and a macrolide or antibiotic; 1 868 received chloroquine, while 3 783 received chloroquine and antibiotics. The remaining 81 144 were in the control group.
The four authors of the study concluded that they did not observe any benefits of chloroquine or hydroxychloroquine when used early after a Covid-19 diagnosis. “Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinical significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with Covid-19,” the study concluded.
The findings of the study made medical experts question whether these two drugs should be used on Covid-19 patients. A number of clinical trials across the global were paused, giving researchers time to look for any safety concerns in relation to the drugs. The WHO’s executive group for the Solidarity Trial decided to temporarily pause the hydroxychloroquine arm of the trial. “This decision was taken as a precaution while the safety data were reviewed by the data safety and monitoring committee of the Solidarity Trial,” the organisation said.
Scrutiny around the study and its findings grew. The authors received criticism from academics questioning the accuracy of the data. More than 100 researchers wrote an open letter to the authors and the editor of The Lancet raising concerns about the statistical analysis and data integrity of the study.
Nel told New Frame that The Lancet study raised a flag about the potential danger of hydroxychloroquine and showed an association between getting the drug and death. “In other words, it showed an association between people getting the drug and them dying,” Nel said.
The study pulled together a lot of patients around the world, compared with early hydroxychloroquine clinical trials in countries such as China, but the researchers did not do randomised trials, in which a group of patients agree to do a trial and are divided into similar groups so the effects of the treatment can be more easily and clearly interpreted.
“What they were doing was a retrospective trial. They were taking it [hydroxychloroquine] when it was given outside of a trial and seeing if they could draw conclusions from that backwards. The important point of it is that the evidence level from that sort of trial when you are doing it backwards, and seeing what happened is a lot lower than the evidence from a randomised trial, which is like [the] Solidarity Trial,” Nel said. “[The study] really does underline again that [hydroxychloroquine] should be given in a trial where the safety monitoring is really good, and where we can answer [the question of its safety and efficacy] probably.”
Last week, The Lancet retracted the study because Surgisphere Corporation, the company that provided the information used in the study, refused to disclose the full data of the clients who participated, claiming it wanted to protect privacy. The information would have been used to conduct a third-party peer review of the study’s findings.
“Based on this development, we can no longer vouch for the veracity of the primary data sources,” The Lancet said in a statement. “Due to this unfortunate development, the authors request that the paper be retracted.”
The WHO has endorsed the operation of all arms of the Solidarity Trial, including hydroxychloroquine. “[This] will apply in South Africa too once the trial gets underway, provided the restarting of the arm is approved by the South African Health Products Regulatory Authority, and assuming there is no new information on hydroxychloroquine before we start,” Nel said.
Medical researchers looked at how hydroxychloroquine affects the cells in a laboratory setting. It showed a lot of promise. “It seemed to interfere with the virus’ ability to replicate and spread. For that reason, it was highlighted as one of the potential candidates to be used.”
Recommendations from the WHO, South African health regulatory bodies and guidelines from around the world all highlight the need to thoroughly study the drug in a trial, rather than just using it in the field without proper testing, Nel noted.
Although hydroxychloroquine has been used on Covid-19 patients in hospitals, “we haven’t enrolled any patients yet. We haven’t used it in a trial at all,” he said.
Prophylactic for healthcare workers
Bruce Biccard, deputy head of the Department of Anaesthesia at the University of Cape Town, said they will soon start a trial that will focus on the effectiveness of chloroquine in protecting healthcare workers from Covid-19.
The trial is run by a group of scientists and physicians under the Covid-19 research outcomes worldwide network (Crown). “It has been approved in the United States of America, United Kingdom, South Africa, Zambia and Ireland,” Biccard said.
They’ve chosen chloroquine because of its accessibility and because it concentrates on the lungs, which makes it a good treatment for Covid-19.
Biccard explained that the focus on frontline healthcare workers is because of the shortage of human resources on the continent. “If healthcare workers get sick with Covid-19, it really attacks the system that provides care. [If they test positive] and they [are] out of the system for two weeks, that has a huge implication,” he said.
He also highlighted the distinction between The Lancet study, in which chloroquine was given in high doses to sick people, and this trial, which will give chloroquine in low doses to healthy participants.
Biccard has linked with hospital and community care researchers to assist them in reaching and covering a large number of healthcare workers in South Africa.