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.
Trauma remains a major cause of mortality and morbidity. 10% of blunt force trauma patients admitted to a major trauma centre will have sustained one or more fractured ribs, which may cause significant pain and problems with breathing.
To establish the outcome of rib fractures and their treatments it is important to know what to measure, and how to measure this accurately. A patient reported outcome measure (PROM) is a questionnaire used to measure patient reported outcomes, to show how the patient is doing from their perspective.
Whilst there is ongoing interest in surgery to fix broken ribs, there is no PROM specifically designed for patients with broken ribs following chest trauma. Therefore, it is not clear whether the symptoms that are most important to these patients are being represented by the current outcome measures. This study aims to create a PROM specific to rib fracture patients to give us a better understanding of whether a new treatment actually makes a difference to the patient’s recovery.
The 1st part of the study involves asking patients with rib fractures to help design a new PROM. This will be conducted through focus groups at a site in Nottingham. The 2nd part of the study entails field testing, whereby patients with rib fractures will be asked to test this new PROM. This will be conducted across multiple secondary care settings in the UK, including the Royal Infirmary of Edinburgh. The study is expected to run for approximately 2 years, with recruitment targets of 50 patients for the PROM Creation phase and 250 for the Field Testing phase.