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MHRA halts recruitment to primary care hydroxychloroquine trial over death reports



Recruitment to an arm of the PRINCIPLE trial – the trial investigating coronavirus (Covid-19) treatments via GP practices – has been halted following concerns about the safety of hydroxychloroquine.

Nearly 800 GP practices across the UK are now recruiting patients onto the trial, led by the University of Oxford, but the World Health Organisation (WHO) has initiated the temporary suspension of global trials that include hydroxychloroquine.

This comes as data from a study published in the Lancet revealed a higher mortality rate in Covid-19 patients treated with hydroxychloroquine – a drug that is most commonly used as an antimalarial.

Professor Chris Butler, lead investigator of the PRINCIPLE trial via the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said: ‘The Medicines and Healthcare products Regulatory Authority (MHRA) has instructed the PRINCIPLE trial of community-based treatments for Covid-19 illness to pause recruitment into its hydroxychloroquine arm. This follows publication of an observational study of hospitalised patients in the Lancet on 22 May 2020.

‘We have therefore temporarily suspended recruitment into the hydroxychloroquine arm of PRINCIPLE. We are working with the MHRA to share as much information as possible to achieve a better understanding of the situation.’

He went on to explain that PRINCIPLE ‘is a flexible, platform trial of interventions suitable for use in the community that may prevent hospitalisation and speed recovery from Covid-19 illness’.

‘In keeping with the generic, flexible trial design, we will continue to evaluate other treatments for Covid-19-like-illness in primary care. The safety of trial participants has always been paramount in PRINCIPLE. Those at greater risk of adverse reactions to study medicines are excluded from taking part.’

Other trials into hydroxychloroquine were also halted, including the World Health Organisation’s ‘solidarity’ trial.

In a media briefing, WHO director-general Dr Tedros Adhanom Ghebreyesus said: ‘The executive group has implemented a temporary pause of the hydroxychloroquine arm within the solidarity trial while the safety data is reviewed by the data safety monitoring board.’

The WHO’s solidarity trial was launched to assess the safety and efficacy of four treatment options against Covid-19, including hydroxychloroquine.

Last week, the study in the Lancet analysed data from nearly 15,000 patients with Covid-19 who received the drug alone or in combination with antibiotics, against a control group of 81,000 who did not receive it.

It found a higher risk of abnormal heartbeats, or arrhythmias, and mortality in patients with Covid-19 treated with hydroxychloroquine.

Dr Ghebreyesus continued: ‘On Friday, the Lancet published an observational study on hydroxychloroquine and chloroquine and its effects on Covid-19 patients that have been hospitalised.

‘The authors reported that among patients receiving the drug, when used alone or with a macrolide, they estimated a higher mortality rate.’

Hydroxychloroquine was developed as an antimalarial drug, but is also used to treat conditions like lupus and arthritis.

US President Donald Trump has said he has been taken hydroxychloroquine, following public hype about it as a potential Covid-19 treatment.

Other studies published this month also suggested that hydroxychloroquine has no effect on the survival rate of Covid-19 patients, and might even increase the risk of adverse effects.

Another recent study found that renin-angiotensin aldosterone system inhibitors – taken by some patients with hypertension – do not impact the severity of Covid-19.

The PRINCIPLE trial is one of several trials supported by the UK Government’s bid to find treatments for Covid-19. They also include the Recovery trial in hospital environments and Remap-Cap trial in intensive care.

Previously, NHS England ‘strongly discouraged’ GPs from prescribing antimalarials while clinical trials into Covid-19 are ongoing.

Meanwhile, antiviral drug Remdesvir this week became the first drug to be approved for treatment of Covid-19 patients in the UK, after it was found to reduce the length symptoms persist.