May 21, 2020

expert reaction to COPCOV trial which will look at whether chloroquine and hydroxychloroquine can be used in prevention of COVID-19 in healthcare settings

The COPCOV trial, being conducted the University of Oxford, will look at whether chloroquine and hydroxychloroquine can be used in prevention of COVID-19 in healthcare settings.

Prof Saad Shakir, Director of the Drug Safety Research Unit (DSRU) in Southampton, said:

“To take a prophylactic medication to prevent an infection in the absence of a vaccine is an acceptable approach, malaria is a well-known example. 

“However, the medicine used for prophylaxis is expected to have demonstrated some clinical activity to treat the condition, in this case Covid-19. 

“We at DSRU have conducted a dynamic systematic benefit-risk evaluation, which included all the information available for the use of chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of Covid-19 (the manuscript is under editorial review). We found the benefit-risk profile of CQ and HCQ is not favourable in the treatment of Covid-19 infection. This raises the question of whether CQ and HCQ will be effective in preventing Covid-19 infection in high-risk people. 

“Another question is for how long would high-risk groups, such as health and social workers, need to take these drugs for; until a vaccine becomes available? We also need to consider whether these drugs will need to be taken by people who have antibodies against Covid-19 (if the antibodies are demonstrated to be prophylactic). Testing health and social care staff for antibodies is part of the UK government’s policy when the antibody testing becomes widely available, and the study design needs to consider this.”

Prof Babak Javid, Principal Investigator, Tsinghua University School of Medicine, Beijing, and Consultant in Infectious Diseases at Cambridge University Hospitals, said:

“There has been a huge amount of media attention on whether the anti-malarial compound chloroquine (CQ) and the related compound hydroxychloroquine (HCQ) have a potential role in the treatment and prevention of COVID-19.  There is some good scientific rationale: both compounds inhibit coronavirus replication in a test-tube (cell culture).  However, no high quality clinical trials in humans have shown any benefit at all, and some potential for harm, especially if HCQ is given in combination with an antibiotic azithromycin.  But, it is possible that those clinical trials were looking for effects in the wrong patient population.  We know that in CVOID-19, viral replication is maximal very early in the disease process.  However, the trials published thus far have all given HCQ to patients many days (more than 1-2 weeks) after symptom onset, which may be too late for HCQ to affect its (potential) beneficial effects.

“This trial aims to address that question: can HCQ prevent COVID-19 infection.  The trial is not looking at treating patients already infected, but whether if taken regularly, it prevents infection in the first place.  It is a high quality design: neither the participants or the trial researchers will know whether an individual is taking HCQ/CQ or placebo (dummy pill).  However, there are some concerns: although rates of infection in healthcare workers (the target population for this trial) was high initially, it appears to have dropped dramatically as we understand COVID-19 transmission better.  If over the course of the trial, not enough participants have become infected by COVID-19 in either ‘arm’ of the trial, it will very hard to perform a rigorous statistical analysis of whether the approach works.  Secondly, it will probably take a long time to get results from this study design.  Although that’s not a fault in the study design in itself, it’s likely that the trial won’t be able to therefore guide practice when it’s needed most: in this first wave of the pandemic over the coming months.

“Nonetheless, the trial is welcome.  COVID-19 treatments have been hampered by poor quality evidence thus far.  We need more rigorous trials such as this to be able to guide therapeutic decision making.”

https://clinicaltrials.gov/ct2/show/NCT04303507

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Saad Shakir: “Saad Shakir is an employee of the Drug Safety Research Unit, an independent charity (No. 327206), which works in association with the University of Portsmouth. He is a member of the Data Safety Monitoring Boards for Diurnal and Biogen.“

Prof Babak Javid: No conflicts

None others received.