UK RECOVERY Trial: Inadequate Hydroxychloroquine Treatment Predictably Fails

While the first results of the UK RECOVERY trials were expected for July, they were unexpectedly released today June 5.

With the epidemic still going strong in the UK, researchers for clinical trials were able to recruit some 11,000 volunteers, all being told and having to consent that there is no treatment for COVID-19.

We covered over 2 months ago how flawed the design of this research was. Yes it’s testing hydroxychloroquine, but not at an early stage, and not in combination with azithromycin and/or zinc.

So it was also pretty much known 2 months ago that no good results were going to come out of this trial.

Despite the fact that it was known that the treatment protocol was sub-optimal, it was left unchanged with thousands of patients being subject to it or to the placebo / usual care alternative.

With 40,261 deaths so far, a case fatality rate of 14.2%, and a mortality of 593 per million of inhabitants, the UK is one of the countries with the worst record in dealing with COVID-19. 

The principal finding released today is:

“A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes.”

On the basis of the reported participation levels and mortality rates in the RECOVERY clinical trials, there were 1132 deaths in this study, for a total number of 4674 participants, i.e. an average fatality rate of 24.2%.

This can be contrasted with the results at the IHU-Marseille, where there were 3,737 patients, including 3,054 treated with Hydroxychloroquine and Azithromycin, and where there was a fatality rate of 0.9%.

How many deaths would have been avoided in this RECOVERY Oxford trial if they had adopted the right treatment protocol? We will never know for sure, but it’s easy to make an estimate on the basis of the differential in the above fatality rates among patients, and it’s pretty devastating.

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What had the “Chief Investigators” of the trial to say?

‘We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalized with COVID-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm of the RECOVERY trial with immediate effect.”

The treatment that was adopted for these trials was: initial intake of 800 mg, then 800 mg 6 hours after the initial intake; another 400 mg 12 hours after intake; another 400 mg 24 hours after initial intake, and then 400 mg every 12 hours during 9 days.

Note the high hospital mortality rates, which shed doubts about the quality of the “usual care” given to UK patients.

Such high mortality in hospitals is not inevitable. If you want to learn about quality hospital care, check for example our interview with Professor Varon, who implements the MATH+ treatment protocol developed in collaboration with the Eastern Virginia Medical Group.

According to Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, “Today’s preliminary results from the RECOVERY trial are quite clear – hydroxychloroquine does not reduce the risk of death among hospitalised patients with this new disease.”

Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, and Chief Investigator for the trial, expressed similar thoughts yet indicated that the focus now would be on other drugs: “Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs.”

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There is not even an attempt to test protocols that are known to work, combining hydroxychloroquine, azithromycin and zinc as an early treatment within days of the first symptoms.

Interestingly, Professor Horby was one of the authors of a large randomized trial conducted in China that showed that remdesivir was not effective in reducing mortality or duration of hospital stay. 

(correction: June 8 ; apparently, the remdesivir arm of the RECOVERY trial did not start because of shortages of the medication)

SEE MEDIA RELEASE

No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19 

PUBLISHED ON JUNE 5 2020

A new statement has been released from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on hydroxychloroquine.

Professor Peter Horby and Professor Martin Landray, chief investigators of the RECOVERY Trial, said ‘In March this year, RECOVERY was established as a randomised clinical trial to test a range of potential drugs for COVID-19, including hydroxycholoroquine.

‘The trial has proceeded at unprecedented speed, enrolling over 11,000 patients from 175 NHS hospitals in the UK. Throughout this time, the independent Data Monitoring Committee has reviewed the emerging data about every two weeks to determine if there is evidence that would be strong enough to affect national and global treatment of COVID-19.

‘On Thursday 4 June, in response to a request from the UK Medicines and Healthcare Products Regulatory Agency (MHRA), the independent Data Monitoring Committee conducted a further review of the data. Last night, the Committee recommended the chief investigators review the unblinded data on the hydroxychloroquine arm of the trial.

‘We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalised with COVID-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm of the RECOVERY trial with immediate effect. We are now releasing the preliminary results as they have important implications for patient care and public health.

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‘A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes.

‘These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19. Full results will be made available as soon as possible.

Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, and Chief Investigator for the trial, said: ‘Hydroxychloroquine and chloroquine have received a lot of attention and have been used very widely to treat COVID patients despite the absence of any good evidence. The RECOVERY trial has shown that hydroxychloroquine is not an effective treatment in patients hospitalised with COVID-19. Although it is disappointing that this treatment has been shown to be ineffective, it does allow us to focus care and research on more promising drugs.’

Martin Landray, Professor of Medicine and Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Deputy Chief Investigator, said, ‘There has been huge speculation and uncertainty about the role of hydroxychloroquine as a treatment for COVID-19, but an absence of reliable information from large randomised trials. Today’s preliminary results from the RECOVERY trial are quite clear – hydroxychloroquine does not reduce the risk of death among hospitalised patients with this new disease. This result should change medical practice worldwide and demonstrates the importance of large, randomised trials to inform decisions about both the efficacy and the safety of treatments.’

Full details of the study protocol and related materials are available at 

http://www.recoverytrial.net

http://www.ox.ac.uk/news/2020-06-05-no-clinical-benefit-use-hydroxychloroquine-hospitalised-patients-covid-19#

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