Social responsibility may be a key reason why researchers are still conducting trials for chloroquine as a Covid-19 treatment despite recent setbacks, says an analyst.
Last month, an international group of researchers began clinical trials to investigate whether the anti-malaria drug could prevent the novel coronavirus, or reduce its severity in front-line healthcare workers.
And this trial looks set to continue — even though the WHO (World Health Organisation) announced on May 25 it was temporarily dropping hydroxychloroquine from its global study of potential Covid-19 treatments due to safety concerns.
Reynald Castaneda, a pharma writer for analytics firm GlobalData, said: “The WHO dropping hydroxychloroquine from its large trial due to safety issues is notable, because the main mantra of clinicians is to do no harm.
“So, even if there is an efficacy signal, the balance between cost and benefit would be even more in the spotlight.
“Despite the setbacks, investigators feel like they have a social responsibility to dig into the clinical value of such drugs, from the conversations I have had with them.
“But, of course, they also told me they appreciate the safety risks, and how potentially unrealistic it may be to complete trials due to a variety of reasons, such as not having enough patients in certain countries.”
Studying chloroquine as a Covid-19 treatment
Researchers from the Washington University School of Medicine in St Louis, Missouri are currently evaluating chloroquine in the CROWN (Covid-19 Research Outcomes Worldwide Network) Coronation trial.
University College London (UCL) in the UK — where data obtained from the trial will be compiled — and Wits University in South Africa are also collaborating in the large-scale study.
It is set to run for the next five months and is enrolling close to 30,000 frontline healthcare workers to take part.
The trial aims to study chloroquine’s ability to prevent Covid-19 infections in healthcare workers or mitigate the severity of the disease in infected people. Researchers also intend to establish the lowest dose that could provide a benefit to patients.
Hydroxychloroquine — a potentially less toxic derivative of chloroquine that is also used to treat malaria — has received increased publicity since US president Donald Trump announced, on 18 May, that he had been taking the drug for “a couple of weeks” as a precautionary measure against Covid-19.
About a week later, the WHO said it was temporarily pausing the hydroxychloroquine arm of its Solidarity trial, which is also testing several other potential coronavirus treatments including remdesivir, and a combination of lopinavir and ritonavir.
WHO director-general Tedros Adhanom Ghebreyesus said this was due to several recent publications detailing concerns around the safety and efficacy of the drug.
One example given on the WHO website is an observational study published in online medical journal The Lancet, which found there was a higher mortality rate among 100,000 patients from multiple countries receiving hydroxychloroquine, or hydroxychloroquine combined with a type of antibiotic called macrolide.
The WHO’s final decision on the efficacy and safety of hydroxychloroquine is expected by mid-June, and will be made once all the data from the Solidarity trial — as well as other ongoing trials and previously published evidence – has been reviewed.
Large-scale clinical trials
The CROWN Coronation trial is set to test chloroquine in multiple locations, including the US, Canada, Ireland, South Africa, Zambia and the UK, while the Solidarity trial is taking place on an even greater scale with more than 400 hospitals in 35 countries actively recruiting patients.
Castaneda believes that, due to the “unprecedented situation” of the Covid-19 crisis, there is an even greater level of international collaboration than ever before within the healthcare industry, as different sites attempt to learn as much as possible from one another.
“Large multi-country trials are fairly typical with late-stage clinical trials, so there are likely systems in place to make them as coordinated as possible,” he added.
“The trend right now, with regards to countries running out of patients for trials, is collaborating with sites in countries that have patients.
“For example, the remdesivir trials started in China, but then went to Europe and the US.
“Also, another approach is that some of these investigators anticipate a second wave in the fall, especially in investigator-led trials that have their trial design as country-specific.”
Castaneda concluded that, while safety concerns around chloroquine may currently be hindering the drug’s potential in treating Covid-19, the situation could yet change because “things are happening at such a rapid pace, and you don’t know what new data will surface tomorrow”.