- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
In hospitalized patients with COVID-19 infection and hypoxia (SaO2 <94% on room air or PaO2:FiO2 <300 mm Hg), does the combination of lopinavir and ritonavir in addition to standard of care decrease the time to clinical improvement?
Lopinavir-ritonavir does not decrease time to clinical improvement and does not reduce mortality in severe COVID-19 infection when compared to standard of care.
At the time of the LOTUS China study, published in March of 2020, there were no proven treatments for COVID-19, and many antiviral agents were investigated. Lopinavir was known to have some in vitro and in vivo activity against SARS-CoV and MERS-CoV, it is combined with ritonavir for increased half-life. A 2004 open-label study suggested some benefits in treating SARS. LOTUS China showed no change between the standard of care with and without lopinavir-ritonavir in time to clinical improvement/hospital discharge or mortality.
- Single-center, open-label, individually randomized, controlled trial
- Lopinavir-ritonavir and standard of care (n=99)
- Standard (n=100)
- Setting: Jin Yin-Tan Hospital, Wuhan, Hubei Province, China
- Enrollment: January 18, 2020 - February 3, 2020
- Mean follow-up: 28 days
- Analysis: Intention-to-treat
- Primary outcome: Time to clinical improvement
- Secondary outcomes:
- Mortality at 28 days
- Detectable viral RNA
- Adult, non-pregnant patients
- RT-PCR positive for SARS-CoV-2
- Pneumonia on imaging
- SaO2 <94% on room air OR
- PaO2:FiO2 <300 mmHg
- Allergy/hypersensitivity to either lopinavir or ritonavir
- Severe liver disease (cirrhosis with AST or ALT >5x ULN)
- Contraindicated medication interactions
- Known HIV infection
- Median age: 58.0 years
- Median NEWS2 score day 1: 5.0
- Mean viral load at day 1 (log10 copies/mL): 4.0
Patients were randomized to lopinavir-ritonavir (400 mg/100 mg) plus standard care or standard care alone
Comparisons are lopinavir-ritonavir with the standard of care vs. standard care alone.
- Time to clinical improvement or discharge from hospital
- 2.11% vs. 2.29% (HR 0.90; 95% CI 0.78-1.04; P=0.16)
"Selected adverse events are shown below; refer to the article for a complete list."
- Any adverse events
- 48.4% vs. 49.5%
- Serious adverse event
- 20.0% vs. 32.3%
- Respiratory failure or ARDS
- 12.6% vs. 27.3%
- 16.8% vs. 12.1%
- The trial population was not blinded, which could influence the clinical decisions that were made and affect the utilized measurements.
- The frequency of glucocorticoid use between the groups was not observed in the trial.
- Funded by Major Projects of National Science and Technology on New Drug Creation and Development
- All authors reported any disclosures or conflicts of interest; see ICMJE Form for Disclosure of Potential Conflicts of Interest for the full listing
- de Wilde AH et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 2014. 58:4875-84.
- Chan JF et al. Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis 2015. 212:1904-13.
- Chu CM et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004. 59:252-6.