PURPOSE:

• There are multiple trials underway to determine efficacy of various treatments for COVID-19
  • Lopinavir/ritonavir is a combination HIV protease inhibitor medication
  • Ribavirin is a nucleoside analogue
• Hung et al. (Lancet, 2020) sought to determine the efficacy and safety of adding interferon beta-1b to lopinavir–ritonavir, and ribavirin for the treatment of COVID-19

METHODS:

• Multicenter, prospective, open-label randomized phase 2 controlled trial (RCT)
  • 6 Hong Kong hospitals | Between February 10 and March 20, 2020
• Participants
  • Hospitalized
  • Confirmed COVID-19
• Study design
  • Randomization (2:1) for a 14 day course of the following
    • Combination group: Combination of lopinavir 400 mg and ritonavir 100 mg every 12 hours | Ribavirin 400 mg every 12 hours | 3 doses of 8 million IU of interferon beta-1b on alternate days
    • Control group: Lopinavir 400 mg and ritonavir 100 mg every 12 h (control group)
• Primary outcome
  • Time for nasopharyngeal swab to be negative for SARS-CoV-2 (using RT-PCR)

RESULTS:

• 127 patients were recruited
  • Combination group: 86
  • Control group: 41
• Median time to symptom onset to start of study treatment: 5 days (IQR 3–7)
• Combination group had a shorter time from treatment to negative swab result (p=0·0010)
  • Combination group: 7 days
  • Control group: 12 days
  • Hazard ratio (HR): 4·37 (95% CI, 1·86–10·24)
• Adverse events
  • No difference between groups
  • Main side effects included limited nausea and diarrhea | Discontinuation of lopinavir–ritonavir in one patient (control group) because of biochemical hepatitis
  • No deaths in either group

CONCLUSION:

• In this phase 2 study, the authors conclude that

…early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19

• Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted

Learn More – Primary Sources:

Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial

Related ObG Topics:

Remdesivir Emergency Authorization: FDA Update and Summary of Preliminary NIH Study Data

NIH COVID-19 Treatment Guidelines

ARDS, Critical Care and COVID-19: ‘Surviving Sepsis Campaign’ Guidelines and Key Points