Lopinavir/ritonavir Lopinavir is an HIV type 1 protease inhibitor. Ritonavir is a CYP3A4 inhibitor that boosts lopinavir concentrations • Open-label RCT comparing lopinavir/ritonavir (99 patients) vs. standard of care (100) in patients with COVID-19 in China. Lopinavir/ritonavir was administered at the dosage of 400/100 mg for 14 days. The primary time-to-event endpoint was clinical improvement from randomization. In the primary study population (ITT), no statistically significant differences were observed with regard to the primary endpoint of clinical improvement (HR 1.24 with standard of care as reference, 95% CI 0.90 to 1.72) and the secondary endpoint of 28-day mortality (19.2% vs. 25.0% in investigational and comparator arms, respectively; percentage difference −5.8%, 95% CI −17.3 to 5.7). In the mITT population, lopinavir/ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care. Median time between symptoms onset and randomization was 13 days (IQR 11–16) [22] • Comparison of lopinavir/ritonavir vs. hydroxychloroquine in patients with mild COVID-19. Open-label RCT (NCT04307693, recruiting). Primary endpoint: virus load at day 3, 5, 7, 10, 14 and 18.
• Comparison of ASC09/ritonavir vs. lopinavir/ritonavir in patients with confirmed COVID-19 pneumoniae. Open-label RCT (NCT04261907, not yet recruiting). Primary endpoint: adverse outcome at day 14 (composite of Spo 2 ≤ 93% without oxygen supplementation, PaO2/FiO2 ≤ 300 mm Hg or respiratory rate ≥ 30 breaths per minute).
• Comparison of lopinavir/ritonavir vs. lopinavir/ritonavir plus umifenovir in patients with COVID-19. Open-label RCT (NCT04252885, recruiting). Primary endpoint: rate of virus inhibition at day 0, 2, 4, 7, 10, 14 and 21.
• Comparison of lopinavir/ritonavir vs. lopinavir/ritonavir plus ribavirin plus interferon beta 1b in patients with COVID-19. Open-label RCT (NCT04276688, recruiting). Primary endpoint: time to negative nasopharyngeal swab RT-PCR (follow-up 30 days).
• Comparison of only supportive treatment vs. lopinavir/ritonavir vs. oseltamivir vs. umifenovir in patients with confirmed COVID-19 pneumonia. Open-label RCT (NCT04255017, recruiting). Primary endpoints: (a) rate of disease remission (mild disease: fever, cough and other symptoms relieved with improved lung CT; severe disease: fever, cough and other symptoms relieved with improved lung CT, Spo 2 > 93% or Pao 2/Fio 2 > 300 mm Hg); (b) time to lung recovery.
• Comparison of chemoprophylaxis with lopinavir/ritonavir vs. placebo in healthcare workers exposed to COVID-19. Double-blind RCT (NCT04328285, not yet recruiting). Primary endpoint: occurrence of a symptomatic or asymptomatic COVID-19 (follow-up 2.5 months).
• Comparison of carrimycin vs. lopinavir/ritonavir or umifenovir or chloroquine in patients with COVID-19 pneumonia. Open-label RCT (NCT04286503, not yet recruiting). Primary endpoints: (a) fever to normal time (follow-up 30 days); (b) pulmonary inflammation resolution time (follow-up 30 days); (c) negative conversion of throat swab RT-PCR at EOT.
• Comparison of lopinavir/ritonavir vs. lopinavir/ritonavir plus xiyanping (injectable component derived from a plant used in traditional Chinese medicine) in patients with COVID-19. Open-label RCT (NCT04295551, not yet recruiting). Primary endpoint: clinical recovery time (follow-up 28 days).
• Comparison of lopinavir/ritonavir plus inhaled interferon alfa vs. lopinavir/ritonavir plus inhaled interferon alfa plus xiyanping injection in patients with COVID-19. Open-label RCT (NCT04275388, not yet recruiting). Primary endpoint: clinical recovery time (follow-up 14 days).
• Comparison of lopinavir/ritonavir plus inhaled interferon alfa vs. lopinavir/ritonavir plus inhaled interferon alfa plus traditional Chinese medicines in patients with COVID-19. Open-label RCT (NCT04251871, recruiting). Primary endpoint: time to complete remission of symptoms (follow-up 28 days).
• Comparison of lopinavir/ritonavir plus hydroxychloroquine vs. lopinavir/ritonavir plus hydroxychloroquine plus levamisole pill plus budesonide plus formoterol inhaler in patients with nonsevere COVID-19 pneumonia. Partly blinded RCT (NCT04331470, not yet recruiting). Primary endpoint: (a) clear CT scan at 3–7 days; (b) negative RT-PCR at 3–7 days.
• Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. losartan vs. placebos in patients with COVID-19. Double-blind, adaptive RCT (NCT04328012, not yet recruiting). Primary endpoint: NIAID COVID-19 ordinal severity scale (follow-up 60 days).
• Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. lopinavir/ritonavir plus interferon beta 1a vs. remdesivir vs. standard of care in patients with COVID-19. Double-blind, adaptive RCT (NCT04315948, recruiting). Primary endpoint: severity rating on a 7-point ordinal scale at day 15.
• Comparison of lopinavir/ritonavir or umifenovir or chloroquine or hydroxychloroquine or oseltamivir (with or without azithromycin) vs. natural honey plus lopinavir/ritonavir or umifenovir or chloroquine or hydroxychloroquine or oseltamivir (with or without azithromycin) in patients with COVID-19. Single-blind RCT (NCT04323345, not yet recruiting). Primary endpoints: (a) positive to negative swabs at day 14; (b) fever to normal temperature in days (follow-up 14 days); (c) resolution of lung inflammation in CT or X-ray (follow-up 30 days).
• Comparison of colchicine (with or without lopinavir/ritonavir) vs. local standard of care in patients with moderate to severe COVID-19. Open-label RCT (NCT04328480, not yet recruiting). Primary endpoint: all-cause mortality (follow-up 30 days).
• Comparison of oseltamivir plus chloroquine vs. oseltamivir plus lopinavir/ritonavir in patients with mild COVID-19 and of lopinavir/ritonavir plus oseltamivir vs. darunavir/ritonavir plus oseltamivir vs. favipiravir plus lopinavir/ritonavir vs. darunavir/ritonavir plus oseltamivir plus chloroquine vs. darunavir/ritonavir plus favipiravir plus oseltamivir in patients with moderate to severe COVID-19. Open-label RCT (NCT04303299, not yet recruiting). Primary endpoint: SARS-CoV-2 eradication time (follow-up 24 weeks).