“Solidarity” is an international clinical trial to help find an effective treatment for COVID-19, launched by the World Health Organization and partners.
The Solidarity Trial will compare four treatment options against standard of care, to assess their relative effectiveness against COVID-19. By enrolling patients in multiple countries, the Solidarity Trial aims to rapidly discover whether any of the drugs slow disease progression or improve survival. Other drugs can be added based on emerging evidence.
Until there is sufficient evidence, WHO cautions against physicians and medical associations recommending or administering these unproven treatments to patients with COVID-19 or people self-medicating with them. WHO is concerned by reports of individuals self-medicating with chloroquine and causing themselves serious harm. WHO guidance on compassionate use can be found here.
On Friday 22 May 2020, The Lancet published an observational study on hydroxychloroquine and chloroquine and its effects on COVID-19 patients that have been hospitalised. The authors reported that among patients receiving the drug, when used alone or with a macrolide, they estimated a higher mortality rate.
The Executive Group of the Solidarity Trial, representing 10 of the participating countries, subsequently met on 23 May 2020 and agreed to review a comprehensive analysis and critical appraisal of all evidence available globally.
The review will consider data collected so far in the Solidarity Trial and in particular robust randomised available data, to adequately evaluate the potential benefits and harms from hydroxychloroquine.
The Executive Group has implemented a temporary pause of the hydroxychloroquine arm within the Solidarity Trial while the safety data is reviewed by the Data Safety Monitoring Board.
The other arms of the trial are continuing. Hydroxychloroquine and chloroquine are accepted as generally safe for use in patients with autoimmune diseases or malaria.
The pressure COVID-19 puts on health systems means that WHO considered the need for speed and scale in the trial. While randomized clinical trials normally take years to design and conduct, the Solidarity Trial will reduce the time taken by 80%.
Enrolling patients in one single randomized trial will help facilitate the rapid worldwide comparison of unproven treatments. This will overcome the risk of multiple small trials not generating the strong evidence needed to determine the relative effectiveness of potential treatments.
Participation in Solidarity
Over 400 hospitals in 35 countries are actively recruiting patients and nearly 3500 patients have been enrolled from 17 countries. Overall, over 100 countries have joined or expressed an interest in joining the trial, and WHO is actively supporting 60 of them with:
- ethical and regulatory approvals of the WHO core protocol;
- identification of hospitals participating in the trial;
- training of hospital clinicians on the web-based randomization and data system;
- shipping the trial drugs as requested by each participating country.
The greater the number of participating countries, the faster results will be generated. WHO is facilitating access to thousands of treatment courses for the trial through donations from a number of manufacturers. WHO is also inviting developers and companies to collaborate on ensuring affordability and availability of the treatment options if they prove effective.
How the Solidarity Trial works
Adults with COVID-19 admitted to participant hospitals can join this study. Eligible patients will be asked to sign to show they understand the possible risks and benefits and consent to joining the study. The medical team responsible for each patient will check whether any of the study treatments would definitely be unsuitable.
After those checks, brief identifying details and any other conditions are digitally recorded for the patient, who is then randomly allocated to one of the study options. This may or may not involve one of the study treatments. Neither the patient nor the medical staff choose which of the study options a patient will receive, as a computer makes this allocation at random.
Critical anonymized information for the trial will only be collected at the randomization stage and when the patient is discharged or dies: which study drugs were given (and for how many days); whether ventilation or intensive care was received (and, if so, when it began), date of discharge, or date and cause of death while still in hospital.
Interim trial analyses are monitored by a Global Data and Safety Monitoring Committee, which is an independent group of experts.
Countries, or particular groups of hospitals, may want to collaborate in making further serial measurements or observations, relating to areas such as virology, blood gases or chemistry and lung imaging. It also possible to incorporate documentation of other aspects of disease status, for example, through linking in electronic healthcare records and routine medical databases. While well-organised additional research studies of the natural history of the disease or of the effects of the trial treatments could well be valuable, they are not core requirements.
Adults (age ≥18 years) recently hospitalised, or already in hospital, with confirmed COVID-19 and, in the view of the responsible doctor, no contra-indication to any of the study treatments will be randomly allocated between
●Local standard of care,
OR local standard of care plus one of
● Lopinavir with Ritonavir
● Lopinavir with Ritonavir plus Interferon beta-1a.
Underlying conditions recorded are: diabetes, heart disease, chronic lung disease, chronic liver disease and asthma, extending to HIV and tuberculosis in the African region.
Severity of illness at entry is determined by recording: shortness of breath, being given oxygen, already on a ventilator, and, if lungs imaged, major bilateral abnormality.