Aspirin is the latest drug to be added to the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, the chair of the trial told British MPs in November 2020.
Giving evidence to a joint inquiry from the House of Commons Science and Technology and Health and Social Care Committees on lessons learnt from the COVID-19 pandemic, Peter Horby, professor of emerging infectious diseases and global health at the University of Oxford, said there was currently a gap in evidence on anti-clotting agents.
“Clotting is a big problem [in COVID-19],” he said. “Aspirin is a widely available, cheap drug which, if it were to work, would be a huge boost.”
Horby explained that the decision to include aspirin was made by the COVID-19 therapeutics advisory panel (CTAP) – a group set up by the Department of Health and Social Care to look at all of the potential therapeutic options for COVID-19.
Each drug being considered for the trial is subject to “rigorous” analysis, said Horby, with “multipage reports on every drug and the evidence base for them”, before they are either “shelved” or recommended to be put forward for the trial.
In his evidence session, Horby also gave updates for progress on the other drugs being testing in the RECOVERY trial, including convalescent plasma, the results for which are expected in six to eight weeks.
Horby also reported that two major companies, including Eli Lilly, had suspended their trials of monoclonal antibodies in hospitalised patients on the grounds of lack of efficacy and potential safety concerns.
He described the trial suspension as “a bit disappointing” but said that he needed to “see more data to ascertain if it was something to worry about”.
Horby also revealed to MPs that it appeared that the case fatality rate in hospitals was half that seen in the first wave of the COVID-19 pandemic.
“Although it’s early days, it would appear that the case fatality rate in hospitals has come down quite a lot — at the moment it’s looking like the case fatality rate is about 15% in hospitalised patients, having come down from about 30% in wave one — so it’s really a big difference.
“We have to be a bit cautious, because the age profile is not the same at the moment — as more older people come in, that will creep up a bit, I think, but it does indicate … that the NHS is getting better at treating COVID patients.”
Horby attributed the reduced fatality rates to “a number of areas of improvement”, including the use of respiratory support, such as oxygen and non-invasive ventilation, as well as intubation and mechanical ventilation.
“Clinicians are getting better at managing that part of the disease and that is improving survival.
“We’re [also] seeing better use of anticoagulants — heparin and others — to prevent clotting, and one would anticipate that the introduction of dexamethasone has also had an impact. That would be something that would reduce fatality rates.”
Earlier study details:
Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report
NEJM study, 17 July 2020
Abstract
BACKGROUND
Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.
METHODS
In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison.
RESULTS
A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
CONCLUSIONS
In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
[link url="https://www.nejm.org/doi/full/10.1056/NEJMoa2021436"]Full findings on the efficacy of dexamethasone in NEJM (Open access)[/link]
[link url="https://www.ukri.org/our-work/tackling-the-impact-of-covid-19/vaccines-and-treatments/recovery-trial-identifies-covid-19-treatments/"]Regularly updated details on the RECOVERY trial (Open access)[/link]