We are conducting a study to find out the best treatments for COVID-19. Several medicines for it have been proposed. These medicines may have no effect or a moderate effect on the disease, but none is expected to have a big effect. This hospital is collaborating through the World Health Organization and hospitals in many other countries in a study to help discover whether any of these treatments can help

Summary Background: WHO helps evaluate drugs by randomising their effects on important outcomes. The WHO Solidarity trial involves collaboration between hundreds of hospitals in dozens of countries. It began by evaluating four repurposed drugs, and now guided by an independent Expert Groups, is now evaluating addition to the local Standard of Care of other potential drugs. Simplicity of procedures: Within each country, the national co-ordinator invites selected hospitals and helps them get ethical and regulatory approval and study drugs, then patient recruitment can begin. To facilitate collaboration even in overloaded hospitals, patient enrolment and randomisation (via a cloud-based GCP-compliant platform) and all other trial procedures are greatly simplified, and no paperwork is required. Once consent has been obtained, electronic entry of anonymised details of a few key characteristics of each patient takes only a few minutes. At the end of patient entry, a random treatment allocation is generated. Eligibility: Adults (age ≥ 18 years), hospitalised with laboratory-confirmed COVID, not expecting transfer within 72 hours, and, in the view of their doctors, with no contra-indication to any potentially relevant study drug. Consent: The study website https://data.castoredc.com/studies has printable patient information in some UN official languages. Once the information has been explained to patients, obtaining consent takes only a few minutes. An electronic image of the signature page is kept (or, if national regulations forbid this, a note to file), and the printed information and original consent stays with the patient or legal representative. Data collected electronically immediately before randomisation: • Country, hospital (from a list of approved hospitals) and randomising doctor • Confirmation that informed consent was obtained from the patient (or a surrogate/ representative) Age, sex and (yes/no): smoking, diabetes, heart disease, chronic liver disease, chronic lung disease, asthma, HIV, obesity • Date of onset of symptoms, date of hospitalization, and (yes/no) current/planned use of a few drugs • Respiratory support (highest level currently being given): A. No oxygen, B. Low-flow oxygen, C. High-flow nasal oxygen, D. Non-invasive ventilation, E. Invasive ventilation, F. ECMO • SpO2 (%) and, if not ventilated, respiratory rate • Any major bilateral lung abnormality? (not imaged/no major abnormality/infiltrations/patchy shadowing) • Which relevant study drugs are locally available? (yes/no: artesunate, infliximab, imatinib; confirm that none of these locally available drug(s) is, in the doctor’s view, definitely contra-indicated) Trial entry; randomization: Once electronic data collection has been completed the patient automatically enters the trial and a random allocation of their trial treatment is generated (by an algorithm that ensures eventual balance in the characteristics just recorded between each study drug and its controls) and displayed. The patients will be randomly allocated either to Standard of Care (SoC) or to one of the study drugs. Changing management of study patients: At all times the patient’s medical team remains solely responsible for decisions about that patient’s care and safety. Hence, if the team decides that deviation from the randomly allocated treatment is appropriate for a particular patient, this should be done, regardless of the random allocation. That patient would still be part of the trial, regardless of what treatment they were actually given.   Safety: Any suspected unexpected serious adverse reactions (SUSARs) that are life-threatening must be reported within 24 hours, as must any other possibly related treatment-related serious adverse events (SAEs). Other adverse events do not need to be reported. Follow-up: When patients die or are discharged, follow-up ceases and their outcome is reported, regardless of whether the trial treatment actually got given. The following information is to be entered: • Which study drug(s) got given (and for how long) • Which of a few selected other drugs were given (and for how long) • What respiratory support was given (and first and last dates): A No respiratory support, B Low-flow oxygen, C High-flow nasal oxygen, D Non-invasive ventilation, E Invasive ventilation, F ECMO • Date discharged alive or date of death in hospital and cause of death. • Pregnant? Yes/No/unknown Primary and secondary analyses: Primary analyses: In-hospital mortality in all patients. Major secondary analyses: In-hospital mortality subdivided by initial respiratory support. Further secondary analyses: duration of hospital stay in lower-risk patients (A-B); and in higher-risk patients (C-F); and initiation of ventilation in lower-risk patients. The main safety analyses will be of reported SAEs possibly related to the treatment and SUSARs. Numbers entered: The larger the numbers entered the more accurate the results will be. If substantial numbers get hospitalised in the participating centres, it may be possible to enter several thousand hospitalised patients receiving no oxygen or low-flow supplemental oxygen, and a few thousand receiving high-flow nasal oxygen, ventilation or ECMO, but realistic, appropriate sample sizes will not be estimated at the start of the trial; the numbers that can be entered will depend on the evolution of the epidemic. Heterogeneity: If a study treatment affects outcome, then this effect could well differ between patients who were receiving different levels of respiratory support when randomised, and separate consideration of these is a secondary analysis. Effects could also differ between younger and older patients, or between patients in one or another country or geographic region. If sufficient numbers are randomised, it may be possible to obtain statistically reliable treatment comparisons within each of several different countries/regions or types of patient. Adaptive design: A global Data and Safety Monitoring Committee will keep the accumulating safety results and major outcome results under regular review. The WHO may recommend adding further treatment arms while the trial is in progress, if evidence emerges that there are suitable candidate therapeutics. Conversely, the WHO may decide to discontinue some treatment arms, especially if the Global Data and Safety Monitoring Committee reports, based on interim analyses, that one or other of the trial treatments definitely does or does not affect mortality. Add-on studies: Particular countries, or particular groups of hospitals, may want to collaborate in making further measurements or observations, such as serial virology, serial blood gases or chemistry, serial lung imaging, or serial documentation of other aspects of disease status of trial patients (perhaps through linkage to electronic healthcare records and routine medical databases). These could be thought of as Phase 2b trials that are being conducted concurrently with the Phase 3 trial. However, while well-organised additional research studies of the natural history of the disease or the effects of the trial treatments could well be valuable, they are not core requirements. Data security: Patient information will be encrypted and held securely by the WHO. Those analysing it will use only anonymised data, and no identifiable patient details will appear in publications. Publication: This international collaboration is co-ordinated through the World Health Organisation. Major findings will be disseminated by the WHO and published in the names of the collaborators.