The WHO Solidarity PLUS Trial will initially evaluate three treatment arms: artesunate, infliximab and imatinib, in addition to the local standard of care.

These drugs were chosen after careful consideration of potential drugs by an independent panel of experts. Based on available data, these drugs were selected for their potential to reduce mortality. 

The drugs were donated by their respective manufacturers for the trial, through Letters of Agreement between WHO and the companies. The companies – Ipca, Johnson and Johnson and Novartis, have agreed to support access to the drugs at reasonable prices if they prove to be effective.

WHO helps evaluate drugs by randomizing their effects on important outcomes. The WHO Solidarity PLUS trial involves collaboration among hundreds of hospitals in dozens of countries. It began by evaluating four repurposed drugs, and now guided by an independent expert group, is evaluating three new drugs in addition to the local Standard of Care.

Simplicity of procedures

Within each country, the national coordinator 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 randomization (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 anonymized 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), hospitalized 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.

Trial entry and 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 local Standard of Care alone or to local Standard of Care plus one of the study drugs.

Primary and secondary analyses

Primary analyses: In-hospital mortality in all patients. Major secondary analyses: In-hospital mortality subdivided by initial respiratory support. The main safety analyses will be of reported SAEs possibly related to the treatment and SUSARs.

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.