Background
Objective
Methods
Criteria for considering studies for this review
Types of studies
Types of participants
Types of interventions
Types of outcome measures
Outcomes
Search methods for identification of studies
Electronic searches
Data collection and analysis
Selection of studies
Data extraction and management
Assessment of risk of bias in included studies
Study | Study type | Score | Percentage | Quality |
---|---|---|---|---|
Çalik BaŞaran et al. [11] | Prospective observational study | 10/14 | 71.4 | Good |
Doi et al. [12] | Case series | 6/9 | 66.66 | Good |
Irie et al. [13] | Case series | 6/9 | 66.66 | Good |
Rattanaumpawan et al. [14] | Retrospective observational study | 8/14 | 57.1 | Fair |
Yamamura et al. [15] | Prospective single center study | 10/14 | 71.4 | Good |
Assessment of heterogeneity
Assessment of reporting biases
Data synthesis
Subgroup analysis and investigation of heterogeneity
Sensitivity analysis
Results
Qualitative synthesis
Study, Year | Population | Intervention | Comparator | Outcome |
---|---|---|---|---|
Cai et al. [18] 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) Resting respiratory rate greater than 30 per minute Oxygen saturation below 93%, oxygenation index < 300 mm Hg 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; 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 |
Calik Basaran et al. [11] 2020, Prospective observational study, Turkey | Total: 174 M: 91, F: 83 Mild: 35 Moderate: 107 Severe: 32 Inclusion criteria Adult patients (More than or equal to 18 years) hospitalized in COVID ward from March 20 to April 30, 2020 Exclusion criteria Critically ill patients with sepsis or ARDS requiring ICU at the time of admission | 32 patients received favipiravir, two patients received favipiravir monotherapy while 30 received it to the initial regimen or with other antivirals 23 patients received HCQ alone while 113 received HCQ + AZT in addition to other supportive treatment | Median time to defervescence days HCQ: 1 (0–4); HCQ + AZT: 1 (0–11); FVP: 3 (0–8) Median time to clinical improvement on therapy HCQ: 1 (1–6); HCQ + AZT: 1.5 (1–11); FVP: 6 (1–10) Median duration LOS HCQ: 2 (1–21); HCQ + AZT: 4 (1–15); FVP: 7.5 (2–24) Nausea/vomiting HCQ: 1; HCQ + AZT: 5; FVP: 5 Elevation of transaminase HCQ: 1; HCQ + AZT: 3; FVP: 10 | |
Chen et al. [19] 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 (> 6 × 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 h 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 care 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: 13/116; C: 15/120 D7 NIMV OR Oxygen support T: 21/116; C:27/120 Total number of adverse reactions T:37/116; C:28/120 Respiratory failure T: 1/116; C: 4/120 No mortalities |
Doi et al. [12] 2020, Case series, Japan | Total: 11 M: 10 F: 1 Comorbidities HTN 4, DM 3, COPD 1 and Cancer 1 Age: 60–69 All patients admitted to ICU 8 patients required MV and 3 required VV-ECMO | Treatment with nafamostat mesylate [0.2 mg per kg per hour by continuous intravenous infusion, median treatment 14 days (IQR, 10 to 14 days)] and FVP [3600 mg on day 1 and at 1600 mg per day on day 2 and subsequently median treatment 14 days (IQR, 12 to 14 days) | Mortality: 1; 7 Patients weaned from MV Discharge from ICU: 9 Discharge from hospital: 7 Adverse effect: 1 (Hyperkalemia) | |
Lou et al. [20] 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(FVP group): 4/9; C: 5/10 Viral negative in Day 14 T(FVP group): 7/9; C: 10/10 Clinical improvement Day 14 T(FVP group): 5/9; C: 5/10 Day 7 T(FVP group): 2/9; C: 1/10 D14 Discharge T(FVP group): 4/9; C: 4/10 Time to clinical improvement—median days (IQR) T(FVP group): 14 (6–38); C: 15 (6–24) Time to viral negative-median days (IQR) T(FVP group): 9 (2–34; C: 9 (1–13) D14 NMV OR Oxygen support T: 3/9; C: 4/10 |
Ivaschenko et al. [21] 2020, Multi center, open label randomized Phase II/ III controlled trial, Russia | Total: 60 Randomization in 1:1:1 in three groups comparable in demographic and baseline characteristics Intention to treat analysis was done Inclusion criteria Hospitalized men and non-pregnant women of 18 years or older who signed the informed consent form, had moderate PCR-confirmed COVID-19 and were able to administrate the drug orally and willing to use adequate contraception during the study and 3 months after its completion | Treatment group One group received either AVIFAVIR 1600 mg BID on Day 1 followed by 600 mg BID on Days 2–14 (1600/600 mg) Other group received AVIFAVIR 1800 mg BID on Day 1 followed by 800 mg BID on Days 2–14 (1800/800 mg) Patients receiving AVIFAVIR did not receive other antivirals or antimalarial drugs | Control group Control group received standard of care according to national guideline 15 patients reveived HCQ or CQ 1 patient received Lopinavir and ritonavir 4 patients did not receive etiotropic treatment | Viral clearance Day 5 TG(FVP group): 25/40; CG: 6/20 Day 10 TG: 37/40; CG: 16/20 Median time to body temperature normalization TG: 2 days (IQR 1–3); CG: 4 days (IQR 1–8) CT improvement at day 15 TG: 36/40; CG: 16/20 Adverse effects TG: 15/40; CG: 5/20 Common side effects were diarrhea, nausea, vomiting, chest pain and increase in liver transaminase levels Early drug discontinuation in 2 patients out of 40 in treatment group Mortality: 2 in TG Discharge AVIFAVIR 1600/600: 13/20 AVIFAVIR 1800/800: 17/20 CG: 17/20 |
Irie et al. [13] 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) | |
Rattanaumpawan et al. [14] 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 h 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 care, 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 care includes protease inhibitors, hydroxychloroquine, azithromycin, steroid, respiratory support, and tocilizumab Control group Patients received standard of care 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) | |
Yammamura et al. [15] 2020, Prospective single center study, Japan | Total: 13 M: 9 F: 4 Mean age: 63 All patients were mechanically ventilated at the time of admission Comorbidities HTN 8, DM 7, Bronchial asthma 1, sleep apnea syndrome 3 | FPV (3600 mg on day 1, 1600 mg from day 2 to day 14), methylprednisolone (1000 mg for 3 days), and low molecular weight (2000 IU every 12 h) or unfractionated heparin (10,000–12,000 IU/day). Methylprednisolone administration was begun on the 5th day from initial FPV administration. Heparin and dexmedetomidine were administered after intubation and mechanical ventilation | Survival: 12 Mortality: 1 Improvement in IL-6 5 days after FPV therapy, PaO2/Fi02 in a week after FVP therapy |