On May 18, 2020, with $9 million from the COVID-19 Therapeutics Accelerator, an international group of physicians and scientists established a research network to evaluate promising therapies for COVID-19. The group, called the COVID-19 Research Outcomes Worldwide Network (CROWN) Collaborative, will test whether the antimalaria drug chloroquine can prevent COVID-19 infection or decrease its severity in front-line health-care workers. An estimated 30,000 such workers from across the globe will participate in the clinical trial, which the collaborative is calling the CROWN CORONATION trial.

The collaborative and the trial are funded 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.

Washington University School of Medicine in St. Louis is the clinical coordinating center for this ambitious international trial. The investigators comprising the CROWN Collaborative are from prominent research organizations in African, European, North American and South American countries, including Cameroon, Canada, Ireland, Ghana, Peru, South Africa, Switzerland, the United Kingdom, the United States, and Zambia.

The study will recruit front-line health-care workers globally, including those from lower- and middle-income countries. That’s important because in many such countries there are relatively few health-care workers per capita, and protecting them from severe COVID-19 infection would provide a substantial public health benefit.

This new trial will be important because of its immense size and global reach, as well as its use of three different but well-established chloroquine dose schedules in healthy people. Health-care workers in the trial will be divided randomly into four groups. Three of the groups will receive chloroquine at various doses. The fourth group will receive an inactive placebo. The researchers want to learn whether the drug can prevent health-care workers from developing COVID-19 disease or decrease the severity of illness for those who do become infected.

The researchers also want to determine the lowest dose required to provide a benefit. Health-care workers in the study will receive lower doses of chloroquine than have been given in most other trials that have focused on treating patients already sick with COVID-19. That is important because lower doses of chloroquine should have fewer side effects. Plus, with a limited supply of chloroquine globally, if a lower dose turns out to be just as effective as a higher dose, many more people could benefit from the drug.

The study will last five months. Health-care workers who participate will take chloroquine or a placebo for the first three months and will be monitored for another two months. Those previously infected with COVID-19 or those who have underlying medical problems that might make it unsafe to take chloroquine, such as heart ailments, will not be eligible to participate.  Data from the trial sites will be compiled at University College London. Laurence Lovat, MD, PhD, a professor of gastroenterology and biophotonics, is the study leader in the United Kingdom.