The World Health Organization has discontinued the Solidarity Trial’s hydroxychloroquine and lopinavir/ritonavir arms as interim results show little or no benefit
WHO has accepted the trial’s International Steering Committee recommendation to discontinue the two trial arms, based on evidence from interim results for hydroxychloroquine vs standard of care and for lopinavir/ritonavir vs standard of care, which showed the two drugs produce little or no reduction in the mortality of hospitalised COVID-19 patients when compared to standard of care.
For each of the drugs, the interim results do not provide solid evidence of increased mortality, said WHO.
There were, however, some associated safety signals in the clinical laboratory findings of the add-on Discovery trial, a participant in the Solidarity trial. These will be reported in the peer-reviewed publication.
The committee also took into account a recent review of evidence from all trials in formulating its recommendation.
Remaining arms in the Solidarity trial currently include treatment with remdesivir and lopinavir/ritonavir with interferon beta-1a.
Remdesivir was previously tested as an Ebola treatment and has reportedly 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.
Meanwhile 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. Interferon beta-1a is used to treat multiple sclerosis.
The WHO’s decision to discontinue the hydroxychloroquine and lopinavir/ritonavir-only arms applies directly to the conduct of the Solidarity trial in hospitalised patients and does not affect the possible evaluation in other studies of hydroxychloroquine or lopinavir/ritonavir in non-hospitalised patients or as pre- or post-exposure prophylaxis for COVID-19.
Interim trial results are now being readied for peer-reviewed publication.
The Solidarity Trial has enrolled patients in multiple countries to compare potential treatments for COVID-19 against standard of care, to assess their relative effectiveness against the disease.
As of 1 July 2020, nearly 5500 patients have been recruited in 21 countries.
The trial randomly allocates 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 between local standard of care, or local standard of care plus one of remdesivir or lopinavir/ ritonavir with interferon beta-1a.
Underlying conditions such as diabetes, heart disease, chronic lung disease, chronic liver disease and asthma, extending to HIV and tuberculosis in the African region, are recorded. Meanwhile 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.