Global trial in healthcare workers tests if malaria drug can prevent COVID-19

Up to 30,000 healthcare workers from across the globe will be recruited to participate in a clinical trial co-led by UCL, which aims to establish whether chloroquine, a widely prescribed anti-malaria drug, could also prevent people from getting COVID-19.

With $9 million in philanthropic support from the ’COVID-19 Therapeutics Accelerator’, the study brings together international physicians and scientists, to form the COVID-19 Research Outcomes Worldwide Network (CROWN) Collaborative.

The trial is being conducted with Washington University in St Louis, USA, and University of the Witwatersrand, South Africa, along with research institutions in Cameroon, Canada, Ireland, Ghana, Peru, South Africa, Switzerland and Zambia. The trial has been granted urgent public health status by the UK’s National Institute for Health Research (NIHR).

Professor Ramani Moonesinghe (UCL Surgery & Interventional Sciences), and NHS England / NHS Improvement’s National Clinical Director for Critical Care, is one of three international chief investigators.

She said: "Around the world, frontline health and care workers are potentially at particularly high risk of contracting the virus due to their regular exposures to the infection. They have also had to continue to work and travel during international lockdowns.

"There is an urgent need to find effective methods of prevention and mitigation. This is particularly important in low and middle income countries where healthcare systems are already over-stretched."

One way of doing this is to find new uses for medicines that are already tried and tested in humans, albeit for different conditions (drug repurposing). Chloroquine has been widely used to prevent and treat malaria and has an extensive safety record.

This international randomised trial, will test whether chloroquine is effective for prophylaxis (drugs used for prevention prior to infection), against the novel coronavirus SARS-CoV-2.

Professor Michael S. Avidan, of Washington University, another of the international chief investigators, said: "When people have to travel to parts of the world where malaria is a problem, they often take low doses of chloroquine to help prevent infection.

"We want to learn whether this drug might work in a similar fashion in the case of COVID-19, or at the very least, whether low-dose chloroquine might help prevent the severe and life-threatening complications associated with the illness."

The ’CROWN CORONATION’ study will recruit frontline healthcare workers globally, including those from lower and middle income countries. Researchers say this is important because in many such countries there are relatively few healthcare workers per capita, and protecting them from severe COVID-19 infection would provide a substantial public health benefit.

In the UK healthcare workers will be recruited from several hospitals, including at University College London Hospitals NHS Foundation Trust. The Health Services Research Centre, based at the Royal College of Anaesthetists, will also assist recruitment.

Professor Laurence Lovat, UK lead investigator (UCL Surgery & Interventional Sciences) said: "Our hypothesis is that chloroquine may decrease the COVID-19 burden by decreasing entry of the novel coronavirus into host cells and by inhibiting viral replication.

"Furthermore, with its anti-inflammatory properties, chloroquine might dampen the exaggerated and unregulated immune response in the host, which often is responsible for the unpredictable and severe complications of COVID-19."

Participants will be randomly assigned to one of four groups: high dose or mid-dose or low dose chloroquine; or a placebo. If the accumulating data demonstrates that the treatment is effective, the placebo arm of the trial might be discontinued at an interim analysis.

Trial statistician, Dr Hakim-Moulay Dehbi (Comprehensive Clinical Trials Unit at UCL), said: "Healthcare workers need to be safe at work and this trial will tell us whether chloroquine could become part of their PPE tool box.

"We aim to find the lowest effective dose, as this would allow the limited global stocks of chloroquine to be spread more widely."

The trial has been funded by the by the ’COVID-19 Therapeutics Accelerator’, an initiative with contributions from an array of public and philanthropic donors, intended to support research and development to bring effective, accessible COVID-19 treatments to market as quickly as possible.

Professor Helen Rees, of the University of the Witwatersrand, and international chief investigator of the trial, said: "In the African region, the healthcare workforce is under-resourced and overstretched, and the impact of the COVID-19 pandemic will make this situation worse.

"If an inexpensive drug such as chloroquine could help protect our health workers it would provide important insurance for many countries whose healthcare systems could collapse if large numbers of healthcare workers were to become infected and could not care for others who were sick with COVID-19."

Professor Moonesinghe, who is also Director of the Health Services Research Centre at the Royal College of Anaesthetists, added: "We’ve all seen the extraordinary response of healthcare workers across the globe in meeting the challenge of COVID-19.

"With the support of the COVID-19 therapeutics accelerator for Africa, and charitable donations to support the trial within the UK and Ireland’s National Health Services, healthcare workers will now also be able to support research which will answer if this safe, inexpensive and widely available drug can be repurposed to prevent severe COVID-19 infection, for worldwide benefit."

Trial note

CROWN CORONATION is a double-blind, randomised, placebo-controlled trial, in which healthcare workers will be randomly assigned to receive one of three different doses of either chloroquine for a period of three months. A fourth group of participants will receive an inert drug (placebo) which will appear unrecognisable from the active drug but will exert no effect. Both the participants and the researchers administering the drugs will not know what they are receiving. This type of experiment is fundamental to medical research and gives us the best chance to see how effective the active drugs are compared to receiving no intervention at all. Healthcare workers will be assessed regularly to detect if they are developing symptoms of COVID-19 or any side effects from the drugs. Innovatively, we will analyse the results as the study progresses, so the amount of healthcare workers assigned to each different dosing group will be adjusted as we learn which treatment might be better.


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