Cai et al [15] 2020, Open label controlled study, China | Total: − 80 T: - 35 C: − 45 Sex: F = 45, M = men (35 of 80) History: Median age (IQR) 47 (35.75–61) Inclusion criteria: • Aged 16–75 years old; nasopharyngeal swabs samples tested positive for the novel coronavirus RNA • Duration from disease onset to enrolment was less than 7 d • willing to take contraception during the study and within 7 d after treatment • no difficulty in swallowing the pills. Exclusion: • Severe clinical condition (meeting one of the following criteria) i) Resting respiratory rate greater than 30 per minute ii) Oxygen saturation below 93%, oxygenation index < 300 mm Hg iii) Respiratory failure, shock, and/or combined failure of other organs that required ICU monitoring and treatment) • Chronic liver and kidney disease and reaching end stages • Previous history of allergic reactions to FPV or LPV/RTV • Pregnant or lactating women • Women of childbearing age with a positive pregnancy test, breastfeeding, miscarriage, or within 2 weeks after delivery; and participated in • Another clinical trial against SARS-CoV-2 treatment currently or in the past 28 d | Treatment group FPV was 1600 mg twice daily on Day 1 and 600 mg twice daily on days 2–14. Medications were given till viral clearance was confirmed or 14 days had passed. Patients received IFN-a1b 60 mg twice daily by aerosol inhalation. | Control group LPV/RTV was LPV 400 mg/RTV 100 mg twice daily. Medications were given till viral clearance was confirmed or 14 days had passed. Patients received IFN-a1b 60 mg twice daily by aerosol inhalation. | Median time of viral clearance T: 4 d (IQR:2.5–9) C: 11 d (IQR:8–13) D8: RT-PCR negative for viral clearance T:26/35 C:17/45 D16: RT-PCR negative for viral clearance T:33/35 C:33/45 CT improvement D4: T:8/35; C:8/45 D9: T:18/35; C:16/45 D14 T:32/35; C:28/45 CT worse D14 T:1/35 C:9/45 Total number of adverse reactions T:4/35 C:25/45 |
Lou et al [16] 2020, Open-label RCT, China | Total: 29 T = 9 and C = 10 T = FPV and C = Control Sex: F = 5, M = 14 History: Median age (SD) T = 58.0 (8.1); C = 46.6 (14.1) Inclusion: All RT-PCR diagnosed Exclusion: Patients who dint complete the dosage of the medication Previous history of malignancy, COPD, renal insufficiency and hepatic insufficiency | Treatment group Baloxavir marboxil or FVP to the current standard antiviral treatment was randomly allocated (1:1:1) FVP group: FVP was used in combination with the existing antiviral treatment. The first dose was 1600 mg or 2200 mg orally, followed by 600 mg each time, three times a day, and the duration of administration was not more than 14 days Baloxavir group: - The dose was 80 mg OD on Day 1 and 4 and if patients are positive it can be given on Day 7 but no more than 3 doses should be given Both groups received existing antiviral treatment including lopinavir/ritonavir (400 mg/100 mg, twice a day orally) or 8 darunavir/cobicistat (800 mg/150 mg, four times a day orally) and arbidol (200 mg, thrice a day orally ) along with interferon-alpha inhalation | Control group Patients received existing antiviral treatment including lopinavir/ritonavir (400 mg/100 mg, twice a day orally) or 8 darunavir/cobicistat (800 mg/150 mg, four times a day orally) and arbidol (200 mg, thrice a day orally ) along with interferon-alpha inhalation. | Viral negative in Day 7 T: 4/9 C: 5/10 Viral negative in Day 14 T: 7/9 C: 10/10 Clinical improvement Day 14 T: 5/9 C: 5/10 Day 7 T: 2/9 C: 1/10 D14 Discharge T: 4/9 C: 4/10 Time to clinical improvement - median days (IQR) T:14 (6–38) C: 15 (6–24) Time to viral negative-median days (IQR) T: 9 (2–34) C: 9 (1–13) D14 NMV OR Oxygen support T: 3/9 C: 4/10 |
Chen et al [17] 2020, RCT, China | Total: 236 T: 116 C: 120 Inclusion • Age 18 years or older • Voluntarily provided informed consent • Initial symptoms were within 12 days • Diagnosed as COVID-19 pneumonia Exclusion • Allergic to FVP or Arbidol • Increased ALT/AST (> 6x upper limit of normal range) or with chronic liver disease (cirrhosis at grade Child-Pugh C) • Severe/critical patients whose expected survival time were < 48 hrs • Pregnant female • HIV infected • Considered unsuitable by researchers for patient’s interest | Treatment Group Patients received FVP (1600 mg, twice the first day followed by 600 mg, twice daily, for the following days plus standard care for 7 days. | Control group Patients received Arbidol (200 mg, three times daily) plus standard of care for 7 days. Standard of cure included traditional Chinese herbal medicine, antibiotics, additional antiviral treatment, immunomodulatory drugs, steroids, psychotic drugs, nutrition support, cardiovascular drugs, supportive oxygen, noninvasive positive pressure ventilation (NPPV) or invasive ventilation | D7 Clinical Recovery T: 71/116 C: 62/120 Clinical deterioration (new dyspnea) T: 4/116 C: 14/120 D7 NMV OR Oxygen support T: 27/120 C:21/116 Total number of adverse reactions T:37/116 C:28/120 Respiratory failure T: 1/116 C: 4/120 No mortalities |
Rattanaumpawan et al [11] 2020, Observational study, Thailand | Total: 247 T: 63 C: 184 Inclusion: Patients aged at least 18 years who had RT-PCR-confirmed SARS-CoV-2 based on a respiratory specimen (nasopharyngeal, oropharyngeal, sputum, endotracheal aspirate, or bronchoalveolar lavage sample) and received at least one dose of FVP. Exclusion: Patients who expired or were discharged within 24 hrs of hospital stay | Treatment group Patients received the median loading dose of FVP of 47.4 (29.1–71.1) MKD along with the standard of cure, and one-third of 176 enrolled patients (33.3%) received a loading dose of ≤ 45 MKD. The median maintenance 177 dose of FVP was 17.9 (10.9–26.7) MKD, and 76.2% of the subjects received a 178 maintenance dose of ≤ 15 MKD. The median duration of FVP therapy was 12 (2–17) days Standard of cure includes protease inhibitors, hydroxychloroquine, azithromycin, steroid, respiratory support, and tocilizumab | Control group Patients received standard of cure including protease inhibitors, hydroxychloroquine, azithromycin, steroid, tocilizumab, and respiratory support. | Outcomes of treatment groups have been only reported. N = 63 Clinical improvement D7: 42/63 No requirement of oxygen supplementation: 25/63 D14: 54/63 No requirement of oxygen supplementation: 27/63 D28: 57/63 No requirement of oxygen supplementation: 27/63 Mortality D14: 1 D28: 3 Adverse drug reaction 39/63 Most common diarrhea (34) and hepatitis (4) |
Irie et al [12] 2020, Case Series, Japan | Total: 7 M: 5 F: 2 Comorbidities HTN: 3 DM: 2 Hyperuricemia: 2 Others included BPH, gout, and fibroid Inclusion: Critically ill patients admitted to ICU under mechanical ventilation | Patients were given 1600 mg FPV on day 1 and 600 mg from day 2–5 | Clinical improvement 3/7 At Day 7 1/7 No requirement for mechanical ventilation: 1/7 At Day 14 3/7 Weaned from mechanical ventilation: 3/7 No oxygenation support: 2/7 Adverse effect 1/7 (Increase in transaminase) |