SARS-CoV-2: Triple Therapy Shortens Viral Shedding Duration in Phase 2 Trial

The results of a phase 2 trial indicate that early antiviral therapy with combined interferon beta-1b, lopinavir–ritonavir, and ribavirin was safe and superior to lopinavir–ritonavir alone in terms of alleviating symptoms and reducing the duration of SARS-CoV-2 viral shedding and hospital stay among patients with mild to moderate COVID-19.

“Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted,” the authors of the trial concluded.

In their multi-center, prospective, open-label, randomized, phase 2 trial, the researchers recruited 127 adult patients with COVID-19 who were admitted to 6 hospitals in Hong Kong, China. Participants were randomly assigned to treatment with a 14-day combination of 400 mg lopinavir and 100 mg ritonavir every 12 hours, 400 mg ribavirin every 12 hours, and 3 doses of 8 million international units of interferon beta-1b on alternate days (combination group; n = 86), or 14 days of 400 mg lopinavir and 100 mg ritonavir every 12 hours (control group; n = 41). Participants in the combination group received the study treatment less than 7 days after the onset of symptoms.

The primary endpoint of the trial was defined as time until receipt of a negative nasopharyngeal swab for SARS-CoV-2 via reverse transcription polymerase chain reaction, which was performed in the intention-to-treat population.

Participants initiated the study treatment a median of 5 days after symptom onset. The results of the study indicated that the median time from the initiation of the study treatment to receipt of a negative nasopharyngeal swab was significantly shorter in the combination group (7 days) compared with the control group (12 days; hazard ratio 4.37).

Furthermore, participants in the combination group experienced complete symptom alleviation in 4 days compared with 8 days in the control group, and had a median hospital stay of 9 days compared with 15 days in the control group.

Adverse events reported during the study included self-limited nausea and diarrhea. No differences in adverse events were observed between the combination and control groups. One participant in the control group discontinued treatment with lopinavir–ritonavir due to biochemical hepatitis.

The researchers noted that no deaths occurred among the study population.

—Christina Vogt

Reference:
Hung IFN, Lung KC, Tso EYK, et al. 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. The Lancet. Published online May 8, 2020. doi:10.1016/S0140-6736(20)31042-4