BANGKOK – The first clinical trial on a massive scale of two antimalarial drugs controversially repurposed for use with Covid-19 patients launches this week to determine their efficacy as a prevention rather than treatment against coronavirus illness.
The aim is to enroll up to 40,000 front-line health workers in Europe, Africa and Asia in the double-blind randomized placebo-controlled study who will voluntarily take either chloroquine or hydroxychloroquine or a placebo for 90 days and make daily reports into a telephone app.
Participants began enrolling in Thailand a week ago and will begin this week in the United Kingdom, with nearly 20 more countries following including Indonesia, Laos, Malaysia and Vietnam.
The largest sample of volunteers will be recruited at multiple sites in the UK. The goal is to give 20,000 people either chloroquine or a placebo and another 20,000 hydroxychloroquine or placebo.
Despite hydroxychloroquine in particular being encouraged as an effective treatment for Covid-19, so far there is only conflicting data from small studies, retrospective reviews and anecdotal interventions in peer-reviewed journals.
Researchers with the Mahidol Oxford Tropical Medicine Research Unit (MORU) based in Bangkok and co-sponsored by the UK’s Oxford University believe there is sufficient indication one or both drugs could inhibit the virus from replicating in cells upon exposure or at least result in less severe illness.
“There are claims these drugs might be beneficial with the Covid-19 infections in either prevention or treatment,” says co-principal investigator and University of Oxford professor Sir Nicholas White. “The truth is, we really do not know if you take them whether you’re better off or worse off. We really don’t know.”
“It’s a big question that needs to be answered. And answers need to be definitive,” he said.
But the MORU researchers believe the drugs hold promise as a prevention partly due to encouraging evidence of their effect on cell cultures. If proven definitively through a large clinical trial as MORU has launched, combined with their low cost and the existing capacity for production, one or both drugs could fill the gap while the world waits for a vaccine.
William Schilling, a research physician and the other co-principal investigator, believes the world is at least a year away from a vaccine and if one of these drugs can be shown to prevent Covid-19, “then it can be used now to potentially save lives.”
And if the results indicate no benefit, the study will still be useful if only to preserve the supply for the millions of people who rely on them for treating lupus and rheumatoid arthritis.
Both drugs are on the World Health Organization’s List of Essential Medicines, which is a compendium of the safest and most effective medicines needed in a health system, as disease-modifying agents used in rheumatoid disorders.
Despite the lack of scientific evidence that it is effective, health workers in a few countries are currently using hydroxychloroquine as a prophylaxis against the disease caused by a new strain of the Severe Acute Respiratory Syndrome–Coronavirus now known as SARS-Cov-2.
As cases of the highly contagious virus escalated globally, a desperate rush to repurpose existing drugs for treatment turned up more than 20 possibilities.
Chief among them were chloroquine and hydroxychloroquine, both approved roughly 70 years ago first to treat malaria and then later lupus and rheumatoid arthritis.
But only small studies on the efficacy of the two drugs for treatment have been reported. Some of them encourage the use of hydroxychloroquine and some warn of cardiac arrest, irreversible retinal damage and toxicity.
The lack of scientific evidence did not stop US President Donald Trump from calling hydroxychloroquine a “game changer” as a treatment in April. Online demand for the drug reportedly rose by as much as 1,000% after Trump’s unscientific claim.
Noting that the drug could cause dangerous heart rhythm abnormalities, the US government’s Food and Drug Administration (FDA) quickly warned that it should be used only in clinical trials or hospitals where patients can be closely monitored.
It is the dosage of the drug and not the drug itself likely causing the side effects, says Schilling. “These drugs have been around a long time. We’re fairly confident with the safety without being complacent.”
In mid-January with the first case of coronavirus outside of China reported in Bangkok, Schilling along with Sir White, a venerable malaria researcher who has worked in Thailand for decades and had written papers on hydroxychloroquine, began pushing for a decisive clinical trial to determine its effectiveness.
The Covid-19 Therapeutics Accelerator, with contributions from the Bill & Melinda Gates Foundation, Wellcome, Mastercard, Madonna and the Chan Zuckerberg Initiative, agreed to fund the global study.
Schilling says that the dosage required for prevention is at least half of what has been typically used with hydroxychloroquine for treating patients.
The MORU-led global study will give health care workers and staff, such as porters and cleaners who are at high risk due to direct contact with people who are infected, one tablet of 155 mg of the base drug a day.
The volunteers will report feeling well or unwell and their temperature twice a day in an app on their phone for three months.
“We won’t know if effective until the results come out,” says Schilling. “We are equally poised to show whether it works or doesn’t. If it decreases the likelihood that people get Covid-19, then great. If it shows no effect, that’s beneficial also. Then we can move on to look at other preventive measures.”