BACKGROUND AND PURPOSE:

• The Solidarity trial is a multinational Phase III-IV clinical trial designed to compare 4 treatments for hospitalized people with severe COVID-19
• Pan et al. (MedRxiv, 2020) present interim results from the Solidarity trial for the following
  • Remdesivir | Hydroxychloroquine | Lopinavir | Interferon-β1a

METHODS:

• Multinational open-label clinical randomized trial
  • 405 hospitals in 30 countries
• Participants
  • COVID-19 inpatients
• Interventions
  • Remdesivir
  • Hydroxychloroquine
  • Lopinavir
    • Fixed-dose combination with Ritonavir
  • Interferon-β1a
    • Initially subcutaneous with Lopinavir
  • Local standard-of-care
• Study design
  • Patients were randomized equally between whichever study drugs were locally available vs control
  • Analysis was with intention-to-treat with pairwise comparisons of each study drug vs its controls
  • Rate ratios (RRs) are stratified for age and ventilation at entry
• Primary outcome
  • In-hospital mortality

RESULTS:

• 11,266 adults were randomized
  • Remdesivir: 2750 patients
  • Hydroxychloroquine: 954 patients
  • Lopinavir: 1411 patients
  • Interferon plus Lopinavir: 651 patients
  • Only Interferon: 1412 patients
  • Standard care: 4088 patients
• Mortality
  • Reported deaths: 1253 patients | Median day 8 (IQR 4 to 14)
  • 28-day mortality: 12%
    • If already ventilated at randomization: 39%
    • Otherwise: 10%
• Death rate ratios (drug vs control)
  • Remdesivir: RR 0.95 (95% CI, 0.81 to 1.11; p=0.05)
  • Hydroxychloroquine: RR 1.19 (95% CI, 0.89 to 1.59; p=0.23)
  • Lopinavir: RR 1.00 (95% CI, 0.79 to 1.25; p=0.97)
  • Interferon: RR 1.16 (95% CI, 0.96 to 1.39; p=0.11)
• There was no clear reduction for the following
  • Mortality (in unventilated patients or any other subgroups)
  • Initiation of ventilation
  • Hospitalization duration

CONCLUSION:

• In the multinational WHO Solidarity trial, remdesivir, hydroxychloroquine, lopinavir and interferon had little or no effect on mortality, length of hospitalization, and ventilation requirement
• The data is published in MedRxiv which means the data is not yet peer reviewed but was released for public analysis
• The authors conclude

The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalisation duration

Narrower confidence intervals would be helpful (particularly for remdesivir), but the main need is for better treatments

Solidarity is still recruiting about 2000 patients per month, and efficient factorial designs will allow it to assess further treatments, such as immune-modulators and specific anti-SARSCov-2 monoclonal antibodies

Learn More – Primary Sources:

Repurposed antiviral drugs for COVID-19–interim WHO SOLIDARITY trial results

Related ObG Topics:

ACTT-1 Remdesivir RCT: Preliminary Results Now Published

COVID-19 Treatment RCT Results: Combination Interferon beta-1b, Lopinavir-Ritonavir and Ribavirin

Meta-analysis of Hydroxychloroquine for the Treatment of COVID-19

Remdesivir for COVID-19: RCT Results from 10 Hospitals in China