“Solidarity” clinical trial for COVID-19 treatments

Caring Female Doctor Holding Hands with Patient Closeup

Source: World Health Organization

“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, the World Health Organization 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.

Rationale

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

The Solidarity trial provides simplified procedures to enable even overloaded hospitals to participate, with no paperwork required. As of April 21 2020, over 100 countries are working together to find effective therapeutics as soon as possible, via the trial.

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.

Treatment options under study

Based on evidence from laboratory, animal and clinical studies, the following treatment options were selected: Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine or Hydroxychloroquine.

Remdesivir was previously tested as an Ebola treatment. It has generated promising results in animal studies for Middle East Respiratory Syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS), which are also caused by coronaviruses, suggesting it may have some effect in patients with COVID-19.

Lopinavir/Ritonavir is a licensed treatment for HIV. Evidence for COVID-19, MERS and SARS is yet to show it can improve clinical outcomes or prevent infection. This trial aims to identify and confirm any benefit for COVID-19 patients. While there are indications from laboratory experiments that this combination may be effective against COVID-19, studies done so far in COVID-19 patients have been inconclusive.

Interferon beta-1a is used to treat multiple sclerosis.

Chloroquine and hydroxychloroquine are very closely related and used to treat malaria and rheumatology conditions respectively. In China and France, small studies provided some indications of possible benefit of chloroquine phosphate against pneumonia caused by COVID-19 but need confirmation through randomized trials.

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

●       Remdesivir

●       Chloroquine or Hydroxychloroquine

●       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. 

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