On 16 June 2020, UK prime minister Boris Johnson hailed a dexamethasone study as the “biggest breakthrough yet” in the fight against coronavirus (Covid-19). There’s no denying the study was a breakthrough that could potentially save many lives.
But the government didn’t tell the whole story. Nor of how a very different outcome to the pandemic could have been achieved given that the drug was successfully trialled elsewhere for a related condition.
Announcement
The Evening Standard reported that an Oxford University trial of dexamethasone suggested that the drug may be the first one that is known to reduce deaths from the virus. Up to a third of coronavirus patients who are on ventilators and a fifth on oxygen would likely survive the disease if taking the drug.
On television, Johnson announced that:
I am proud of these British scientists [at Oxford], backed by UK Government funding, who have led the first, robust clinical trial anywhere in the world to find a coronavirus treatment proven to reduce the risk of death.
What Johnson failed to mention was that dexamethasone had been trialled in Spain as part of a much longer though smaller study. Nor how an identical trial in Brazil had commenced in March 2020, the same time as the Oxford trial began. Instead, Johnson’s statement was all about Britain and the available supply of the drug. The UK has 200,000 courses, stockpiled since March.
The UK trial
The Oxford-based Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial commenced 19 March 2020, but not publicised by the government until 3 April.
The RECOVERY chief investigators released a statement, reporting that:
Dexamethasone reduced deaths by one-third in ventilated patients… and by one fifth in other patients receiving oxygen only… There was no benefit among those patients who did not require respiratory support…
Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.
It added:
Overall dexamethasone reduced the 28-day mortality rate by 17%.
The RECOVERY trials were listed with the EU Clinical Trials Register as a randomised controlled trial. Patients admitted to the trials had to be aged at least 18 years, in hospital, suspected of contracting coronavirus, and without a history that might put the patient at significant risk.
As well as low dose dexamethasone, RECOVERY is also examining other treatments: Lopinavir-Ritonavir (used to treat HIV), Azithromycin (an antibiotic), Tocilizumab (an anti-inflammatory) and convalescent plasma (from coronavirus survivors).
Coronavirus and ARDS
It’s important to understand the connection between coronavirus and ARDS.
According to a paper in the Medical Journal of Australia:
Severe coronavirus disease 2019 (COVID-19) represents viral pneumonia from SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection leading to acute respiratory distress syndrome (ARDS).
It added:
Its manifestations can be viewed as a combination of the two processes, namely viral pneumonia and ARDS.
The Scientist explains further:
ARDS is a syndrome with different causes, including pneumonia, sepsis, and inhalation injuries. Symptoms include shortness of breath, faster respiratory and heart rates, and dangerously low blood oxygen levels.
However, critical care physician Bram Rochwerg adds how “COVID—in the extreme case—can cause ARDS, and that’s why people die predominantly”.
Other trials
In March 2020, Brazil registered its trial of coronavirus-associated ARDS treated with dexamethasone. It explains that: “around 5% of all patients [with Covid] develop Acute Respiratory Distress Syndrome (ARDS), which is the leading mortality cause in these patients”.
Published trial from Spain endorses Oxford study. https://t.co/t7SYkKR33R
— Anthony Costello (@globalhlthtwit) June 17, 2020
As former WHO director Anthony Costello recently pointed out, a February 2020 paper in the Lancet referred to a multi-centre randomised controlled trial of dexamethasone in Spain between March 2013 and December 2018. Details were first published in February 2020. The study was about the treatment of ARDS to “assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality”.
The Spain-based trial concluded, “In patients with established moderate-to-severe ARDS administered intravenous dexamethasone, we observed a reduction in the number ventilator-free days of more than 4 days and a 15% increase in the 60-day survival compared with patients in the control group”. Also: “Early administration of dexamethasone could reduce the duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS”.
Drug already in widespread use in Spain
That conclusion is not miles apart from that of the later RECOVERY conclusion. And that might explain why apparently dexamethasone has been used in Spain to treat patients with coronavirus since February 2020:
Hate to burst his bubble but we have been using it in Spain since February . https://t.co/sONQbFdcw2
— Spanish Dan 💙 conservative CORRUPTION (@SpanishDan1) June 17, 2020
Indeed, Science reports that: “In places like Spain, dexamethasone has already been widely used against COVID-19”.
Exceptionalism?
The Oxford-based trial was large scale, involving more than 6,000 patients in 175 hospitals. It’s clearly a success story. But no one in UK government, including the prime minister, acknowledged similar trials that had taken place elsewhere. The Spain-based trial, in particular, was able to offer useful conclusions and may explain why dexamethasone is apparently already widely used in that country to treat patients with coronavirus.
The Oxford-based trial was ended prematurely because “sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit”. Though a more cynical explanation for the timing of the announcement may have something to do with pharma shares and subsequent profits. Importantly, researchers argue that had the drug been administered earlier in the pandemic, around 5,000 lives may have been saved.
