Triple Combination of Lopinavir–Ritonavir, Ribavirin, and Interferon Beta-1b in the Treatment of Patients With COVID-19 - Triple Combination for COVID-19 Treatment

May 18, 2020
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.
Date Published:
05/08/2020
Date Updated:
05/18/2020
Original Posted Date:
05/18/2020
References

Contribution To Literature:

This trial showed that triple combination antiviral therapy was superior to control at shortening the duration of COVID-19 viral shedding.

Description:

The goal of the trial was to evaluate triple combination antiviral therapy compared with control antiviral therapy among patients admitted to Chinese hospitals with COVID-19 infection.

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients admitted to Chinese hospitals with COVID-19 infection were randomized to triple combination therapy oral lopinavir 400 mg/ritonavir 100 mg twice daily, ribavirin 400 mg twice daily, and subcutaneous injection of interferon beta-1b (1-3 doses on alternating days) (n = 86) versus control therapy oral lopinavir 400 mg/ritonavir 100 mg twice daily (n = 41). For patients recruited between 7 and 14 days of symptom onset, interferon beta-1b was omitted.

  • Total number of enrollees: 144
  • Duration of follow-up: 30 days
  • Mean patient age: 51 years
  • Percentage female: 48%
  • Percentage with diabetes: 13%

Inclusion criteria:

  • Patients ≥18 years of age admitted to the hospital with COVID-19 infection (diagnosed by reverse transcriptase polymerase chain reaction [RT-PCR])
  • A national early warning score 2 (NEWS2) of ≥1
  • Symptom duration of ≤14 days upon recruitment

Principal Findings:

The primary outcome, median time to achieve a negative nasopharyngeal swab sample, was 7 days in the triple therapy group compared with 12 days in the control group (p = 0.001).

Secondary outcomes:

  • Median time to resolution of symptoms defined as a NEWS2 of 0 and maintained for 24 hours: 4 days in the triple therapy group compared with 8 days in the control group (p < 0.001)
  • Median hospital stay: 9 days in the combination group vs. 14.5 days in the control group (p = 0.016)
  • Adverse events: 48% of the triple therapy group vs. 49% of the control group (diarrhea was the most comment adverse event)

Interpretation:

Among patients with COVID-19 infection, triple antiviral therapy was associated with a shortening in duration of viral shedding compared with control therapy. Triple antiviral therapy was associated with a shortening of hospital duration and also with a reduction in NEWS2 score. This scoring system determines the degree of illness of a patient and prompts critical care intervention, as appropriate. The antiviral agents evaluated in this trial were known to have modest antiviral activity against related coronaviruses. When these agents were used together as triple therapy against COVID-19, they appeared to be associated with synergistic antiviral effects.

References:

Hung IF, Lung KC, Tso EY, 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. Lancet 2020;May 8:[Epub ahead of print].

Clinical Topics: COVID-19 Hub, Prevention, Statins

Keywords: Combined Modality Therapy, Coronavirus, COVID-19, Diarrhea, Interferons, Length of Stay, Lopinavir, Primary Prevention, Reverse Transcriptase Polymerase Chain Reaction, Ribavirin, Ritonavir, severe acute respiratory syndrome coronavirus 2, Virus Shedding


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