June 5, 2020

expert reaction to the RECOVERY trial reporting no clinical benefit from use of hydroxychloroquine in patients admitted to hospital with COVID-19

The Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial have announced that they will no longer be enrolling participants in the hydroxychloroquine arm of the trial after data has shown no clinical benefit from use of hydroxychloroquine in patients admitted to hospital with COVID-19.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine (LSHTM), said:

“This press release is an example of clarity. It shows that the randomised data from this carefully conducted trial have been appropriately monitored and have now been reported clearly.

“The numbers and the estimates of the effect of hydroxychloroquine in hospitalised patients are shown very well. The basic message is that, although hydroxychloroquine is not shown to be strongly harmful, it is reasonably clear that any benefit would, at best, be only minimal. If there is something other than no effect, it is very much more likely to be harmful. The need for randomised trials is illustrated so well by this trial. The conclusions are clear and we await further results that will show whether others of the treatments have benefits.

“It will be good to have confirmation from the other randomised trials involving hydroxychloroquine to show that it does not have benefit in treatment, and to be able to characterise that it is equally of no benefit given early or late in the course of disease.

“This does not absolutely rule out a possible benefit for hydroxychloroquine in prevention of COVID-19 – such a benefit is logically possible, but it is most unlikely. It is also vital to ensure that in giving hydroxychloroquine to otherwise healthy people, it causes ho harm.”

Dr Nick Cammack, COVID-19 Therapeutics Accelerator Lead at Wellcome:

“It is disappointing that hydroxychloroquine has no benefit in patients hospitalised by COVID-19, but negative results are still extremely valuable. This large-scale clinical trial has provided researchers around the world with an answer on the effectiveness of this drug in this setting.

“Wellcome has funded prophylaxis studies on hydroxychloroquine and chloroquine, which aim to understand whether the drugs can prevent COVID-19 in healthy patients when taken at approved dosage levels. By looking at a different population group, stage of disease and dosage, we may see significantly different results to those from the RECOVERY trial.

“Taken at the right dosage, hydroxychloroquine and chloroquine are safe and effective treatments for malaria, but COVID-19 is a new disease. Only through large-scale clinical studies can we understand how it responds to different treatments. But we must be realistic; drugs like hydroxychloroquine may not be the answer. It is essential that governments, businesses and philanthropists take the financial risk and invest in a wide range of potential treatments now, alongside vaccines and testing.”

Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:

“This is a really important result, at last providing unequivocal evidence that hydroxychloroquine is of no value in treatment of patients hospitalised with COVID-19. It’s quite toxic, so stopping treatment with this compound will be a great benefit to patients. The full results of the trial will take time to analyse and report, but it is a great credit to the investigators that they held on and continued the study despite the conflicting evidence from elsewhere.

“Proper studies done at scale are the only way to find out if a treatment should be used or not, and this clearly tells us that hydroxychloroquine is not to be used in those with COVID-19. The ability of the investigators to rapidly recruit 4,674 patients to this study from NHS hospitals in a coordinated national consortium shows what a good environment we have for clinical investigation in the UK. It also shows that the support from non-commercial funders has a vital role in producing independent data that has immediate benefits to patients.

“Everyone regrets that it doesn’t work, but knowing that allows us to focus on finding drugs that actually help recovery from COVID-19.”

Prof Ian Hall, Professor of Molecular Medicine, and Director of the Nottingham Biomedical Research Centre, University of Nottingham, said:

“It is extremely helpful that the RECOVERY team have released their analyses of treatment of COVID-19 with hydroxychloroquine given the recent retraction of The Lancet study suggesting hydroxychloroquine might actually be harmful in the treatment of this condition. I think the RECOVERY study data provides clarity on what has been a contentious issue, i.e. whether or not hydroxychloroquine is useful in treating COVID-19. The RECOVERY data show definitively that hydroxychloroquine is not an effective treatment for COVID-19. Because hydroxychloroquine can cause significant side effects (especially in the heart), its use to try and treat patients admitted to hospital with COVID-19 should be avoided.”

Prof Parastou Donyai, Director of Pharmacy Practice and Professor of Social and Cognitive Pharmacy, University of Reading, said:

“People running the RECOVERY trial, a large scientific experiment testing different drugs for COVID-19 in hospitals, have stopped giving people hydroxychloroquine. They have done this because all their tests showed that it did not give people any better chances of surviving COVID-19. And people did not end up spending fewer days in hospital, or get any other benefits from taking hydroxychloroquine compared to the care they would usually receive.

“This news, although not positive, is a welcome relief to thousands of scientists, doctors and academics who have been crying out for proper proof of whether hydroxychloroquine works in COVID-19 or not. Hydroxychloroquine was propelled onto the world stage by President Trump, who not only sang its praises without solid evidence, but also claimed to be taking the drug himself. The RECOVERY trial continued to test hydroxychloroquine even though another trial using the drug was briefly stopped by the WHO after a much-criticised Lancet paper reported huge side-effects with the drug.

“Continuing to test hydroxychloroquine in this way was a wise decision as it now gives the definitive proof needed: hydroxychloroquine does not work in COVID-19 and should not be used.”

Prof Ravi Gupta, Professor of Microbiology at the University of Cambridge, said:

“These results from an interim analysis of the RECOVERY trial show that hydroxychloroquine did not have a significant mortality benefit over standard of care in patients hospitalised with suspected COVID-19 disease. These are important data for the world, but we must see the data properly peer reviewed without delay.”

Prof Francois Balloux, Professor of Computational Systems Biology and Director of UCL Genetics Institute, University College London (UCL), said:

“The RECOVERY randomised clinical trial looks sound. The absence of any meaningful benefit of hydroxychloroquine in the treatment of COVID-19 infections is in line with other comparable clinical trials.”

Prof Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases, University of Nottingham, said:

“The real story for the press is that the UK is leading the way in recruiting patients into proper randomised controlled trails and now stands at over 11,000. Many other countries around the world have not been so organised – if they had, we would have even more results as to what works and what does not.”

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

“The UK’s RECOVERY trial is a high quality trial in that it is a double-blind randomised controlled trial. The trial has recruited over 11 000 patients to several different arms (treatments, or placebo). Today, the preliminary analysis of just the hydroxychloroquine (HCQ) arm was reported in a press release.

“About 1500 hospitalised patients receiving HCQ were compared with 3100 patients receiving no specific drug in the trial. Over 80% of patients have completed follow-up, i.e. either recovered or died. HCQ was not associated with any significant benefit in terms of effects on death rates, recovery time or other parameters, nor was it associated with any harm. The latter point is relevant given the recent scandal with regards to the now retracted paper published in The Lancet in May showing HCQ therapy increased mortality in COVID-19 patients.

“This is the first strong and robust evidence that HCQ does not work for COVID-19 under these circumstances. However, it should be noted that in the UK, hospitalised patients are usually at least a week into their illness. From what we know about COVID-19, viral replication is very much on the decline at that point, and therefore it is not too surprising, given that HCQ was investigated for its potential anti-viral activity, that it did not work in these patients. Definitive evidence on whether HCQ works in early COVID-19 disease is still lacking. But these new data should now mean moderate to severely ill patients with COVID-19 should not be started on HCQ.”

Prof Graham Cooke, NIHR Research Professor, Imperial College London, said:

“These first results from the RECOVERY trial are very helpful. Although it shows no benefit from treatment with hydroxychloroquine, it will prevent many people being treated with a drug that is potentially harmful, particularly in high doses. Furthermore, it will allow patients now recruited into the trial the opportunity to access treatments that may be able to improve outcome, such as low dose steroids and convalescent plasma. The results highlight the value of large strategic trials that can produce results quickly in time for them to change practice during the pandemic.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“Hydroxychloroquine has been the subject of numerous smaller trials and a recent controversial study that was retracted from The Lancet. It has also been used off-label and promoted by various sources as an effective treatment for SARS-CoV-2 infection.

“What has been missing is reliable and extensive data from a randomised clinical trial that could report convincingly on efficacy. This report from the RECOVERY trial achieves this very aim. As Professor Horby mentions, whilst it is always disappointing to have a prospective therapy fail to provide benefit, especially amidst the current crisis, we do now at least have clarity on this issue. Ideally now efforts can focus on other promising therapies.

“Interestingly, no mention of adverse effects or increased mortality is included in this announcement, casting more doubt upon the validity of the data provided to the authors of The Lancet study by a commercial partner. The value of studies such as RECOVERY during the present situation cannot be understated.”

https://www.recoverytrial.net/files/hcq-recovery-statement-050620-final-002.pdf

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/COVID-19

Declared interests

Prof Stephen Evans: “No conflicts of interest. I am funded (1 day/week) by LSHTM. They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator or any grants obtained from them. I am the statistician to the “meta-Data Safety and Monitoring Board” for CEPI. I will probably be paid for my attendance at meetings and expenses for travel.”

Dr Nick Cammack: “The RECOVERY trial receives core funding from Wellcome.”

Prof Parastou Donyai: None to declare

Prof Ravi Gupta: None to declare

Prof Graham Cooke: “I am a local investigator on Recovery”

Dr Stephen Griffin: None to declare

None received.