In 2019 a novel coronavirus-induced disease (COVID-19) emerged in Wuhan, China. A month later the Chinese Center for Disease Control and Prevention identified a new beta-coronavirus (SARS coronavirus 2, or SARS-CoV-2) as the aetiological agent. The clinical manifestations of COVID-19 range from asymptomatic infection or mild, transient symptoms to severe viral pneumonia with respiratory failure. As many patients do not progress to severe disease the overall case fatality rate per infected individual is low, but hospitals in areas with significant community transmission have experienced a major increase in the number of hospitalized pneumonia patients, and the frequency of severe disease in hospitalised patients can be as high as 30%. The progression from prodrome (usually fever, fatigue and cough) to severe pneumonia requiring oxygen support or mechanical ventilation often takes one to two weeks after the onset of symptoms. The kinetics of viral replication in the respiratory tract are not well characterized, but this relatively slow progression provides a potential time window in which antiviral therapies could influence the course of disease.
There are currently no approved anti-viral or host-directed treatments for COVID-19. This study allows reliable assessment of the effects of multiple different treatments (including re-purposed and novel drugs) on major outcomes in COVID-19. All patients will receive usual care for the participating hospital.
First (main) randomisation
No additional treatment: There are currently no approved anti-viral or host-directed treatments for COVID-19.
Lopinavir-Ritonavir: Lopinavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor, which is combined with ritonavir to increase lopinavir’s plasma half-life. Lopinavir-Ritonavir has shown activity against SARS and MERS CoVs.
Low dose corticosteroids: Favourable immune response modulation by low-dose corticosteroids might help treat severe acute respiratory coronavirus infections, including COVID-19, SARS and MERS.
Hydroxychloroquine: Hydroxychloroquine, a derivative of chloroquine, has been used for many decades to treat malaria and rheumatological diseases. It has antiviral activity against SARS-CoV-2 in cell culture.
Azithromycin: Azithromycin is a macrolide antibiotic with immunomodulatory properties that has shown benefit in inflammatory lung disease.
Second randomisation for patients with progressive COVID-19
Severe COVID-19 is associated with release of pro-inflammatory cytokines, such as IL-1, IL-6 and TNFα, and other markers of systemic inflammation including ferritin and C-reactive protein.3,5,6 There is a possibility that this response may cause or exacerbate lung injury, leading to life-threatening disease.
Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second randomisation between the following treatment arms:
No additional treatment: There are currently no approved immunomodulatory or other host-directed treatments to prevent the progression of COVID-19.
Tocilizumab: Tocilizumab is an interleukin-6 (IL-6) receptor antibody which blocks a
component of the immune response that may drive progression to ARDS.
Additional information can be found on the official trial website: https://www.recoverytrial.net/
Honorary Professor of Emergency Medicine & Clinical Director of the Emergency Department
Assisting in identifying patients with Humeral shaft fractures in the ED by screening.
Giving patient information sheets to introduce the study, so patient has had adequate time to read and make decision about going into the trial before going to the fracture clinic.
DASH is a randomised clinical trial investigating a treatment to reverse the effects of blood-thinning medications.