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Table 2 Study and patient characteristics

From: Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

Author Study name Study design Inclusion criteria Exclusion criteria Interventions Patient characteristics Patient allocation
Favipiravir
Bosaeed et al. [40] Favipiravir and Hydroxychloroquine Combination
Therapy in Patients with Moderate to Severe COVID-
19 (FACCT Trial): An Open-Label, Multicenter,
Randomized, Controlled Trial
OLRCT • ≥ 18 years of age
•Not pregnant
•Diagnosed
•with COVID-19 confirmed by RT-PCR
•Admitted patients with moderate-to-severe COVID-19 (SaO2 of ≤ 94% while breathing ambient air or
•significant clinical symptoms with chest x-ray change)
•Enrolled within 10 days of disease onset
•Written informed consent
•History of myocardial infarction or irregular rhythm/
•QTc in the baseline
•ECG of > 490 ms
•Comorbidities such as: hematologic malignancy,
•advanced (stage 4–5) CKD or dialysis therapy, severe liver damage (Child-
•Pugh score ≥ C, AST > five times the upper limit), or HIV
•HCQ + FVP (n = 125)
•D1: 1800 mg FVP + 400 mg HCQ, 2x/day
•D2-10: 800 mg FVP 2x/day
•D2-D5: 200 mg HCQ 2x/day
•Also received SoC
•SoC (n = 129)
•Included other antivirals
•HCQ + FVP (n = 125)
•Age, years: 53.03 ± 12.79
•Male: 75 (60%)
•WBC, cells/nL 7.77 ± 3.63
•Time Sx onset to Tx start, days: 5.96 ± 2.05
•SoC (n = 129)
•Age, years: 52.27 ± 13.36
•Male: 76 (58.91%)
•WBC, cells/nL 7.54 ± 3.32
•Time Sx onset to Tx start, days: 5.75 ± 2.07
•HCQ + FVP:
•Randomized: 132
•Included in outcome analysis: 125
•SoC:
•Randomized:136
•Included in outcome analysis: 129
Chen et al. [25] Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial OLRCT • ≥ 18 years of age
•Diagnosed as COVID-19 pneumonia according to the Chinese Diagnosis and Treatment Protocol
•COVID-19 could be diagnosed without a positive SARS-CoV-2 nucleic acid test result by: (1) a positive chest CT scan; (2) significant clinical manifestation (3) laboratory results indicating lymphopenia
•Enrolled within 12 days of initial symptoms
•Voluntarily provided informed consent
•Allergic to FVP or ARB
•Elevated 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
•HIV infection
•Considered unsuitable by researcher
•FVP (n = 116)
•D1: 1600 mg FVP 2x
•D2-7: 600 mg FVP 2x/day
•ARB (n = 120)
•200 mg ARB 3x/day
•7–10 days
•FVP (n = 116)
•Age, years:
• < 65 years: 87 (75.00%)
• ≥ 65 year: 29 (25.00%)
•Male: 59 (50.86%)
•ARB (n = 120)
•Age, years:
• < 65 years: 79 (65.83%)
• ≥ 65 years: 41 (34.17%)
•Male: 51 (42.50%)
•FVP:
•Randomized: 120
•Included in outcome analysis: 116
•ARB:
•Randomized:120
•Included in outcome analysis: 120
Dabbous et al. [41] Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study OLRCT •18–80 years of age
•Confirmed SARS-CoV-2 infection with mild or moderate symptoms
•Hospital admission three days after the symptom onset
•Agreed to participate in the study and signed an informed consent
•Allergic or contraindication to the drug
•Pregnant or lactating
•Cardiac problems
•Liver or renal failure
•Other organ failure
•FVP (n = 44)
•D1: 1600 mg FVP 2x/day
•D2-10: 600 mg FVP 2x/day
•Also received SoC
•CQ (n = 48)
•D1-10: CQ 600 mg tablets 2x/day
•Also received SoC
•FVP (n = 44)
•Age, years: 34.86 ± 15.95
•Male: 20 (45.5%)
•WBC, cells/nL 6.58 ± 2.99
•CQ (n = 48)
•Age, years: 36.15 ± 17.67
•Male: 25 (52.1%)
•WBC, cells/nL 5.60 ± 2.61
•FVP
•Randomized: 48
•Included in outcome analysis: 44
•CQ
•Randomized: 48
•Included in outcome analysis: 48
Doi et al. [48] A Prospective, Randomized, Open-Label Trial of Early versus Late
Favipiravir Therapy in Hospitalized Patients with COVID-19
OLRCT • ≥ 16 years of age
•Inpatient status
•Positive
•RT-PCR for SARS-CoV-2 from a pharyngeal or nasopharyngeal swab specimen collected within 14 days
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (12)
•Ability to remain
•hospitalized for 6 days or longer
•Negative pregnancy test (premenopausal female only)
•Written consent for participation
•Performance status of 2 or greater
•Severe hepatic disease
•Need for dialysis
•Altered mental status
•Pregnancy
•Female patients who did not agree to
•use effective contraceptive methods
•Male patients with female partners who did not agree to the
•use of effective contraceptive methods
•Hereditary xanthinuria
•Hypouricemia or history of
•xanthine urolithiasis
•Uncontrolled gout or hyperuricemia
•Immunosuppressive conditions
•Receipt of systemic antiviral agent against SARS-CoV-2 within 28 days
•Early treatment FVP (n = 44)
•D1: 1800 mg FVP 2x/day
•D2-10: 800 mg 2x/day
•Late treatment FVP (n = 44)
•D6: 1800 mg FVP 2x/day FVP
•D6-16: 800 mg 2x/day
•Early treatment FVP (n = 44)
•Age, years: 48.0 (34.5, 68.0)
•Male: 23 (52.3%)
•SpO2 adm: 96.0%
•WBC, cells/nL: 4.4 (3.6, 5.8)
•Time Sx onset to Tx start, days: 7.0 (5.5, 10.0)
•Late treatment FVP (n = 44)
•Age, years: 51.0 (39.5, 62.0)
•Male: 31 (70.5%)
•SpO2 adm: 96.0%
•WBC, cells/nL: 5.1 (4.0, 6.4)
•Time Sx onset to Tx start, days: 8.0 (5.0, 10.0)
•Early FVP
•Randomized: 44
•Included in outcome analysis: 44
•With positive RT-PCR on D1: 36
•Late FVP
•Randomized: 45
•Included in outcome analysis: 44
•With positive RT-PCR on D1: 33
Lou et al. [30] Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: An Exploratory Randomized,
Controlled Trial
OLRCT • ≥ 18 years of age
•voluntarily provided informed consent
•Confirmed COVID-19 infection by RT-PCR
•No difficulty swallowing oral drugs
••Ability to follow protocol according to the judgment of researchers
•Allergic to any related drugs
•Weight < 40 kg
•Critical illness (respiratory failure and mechanical ventilation, shock, other organ failure requiring ICU treatment)
•Renal insufficiency (estimated creatinine clearance < 60 ml/min)
•Abnormal laboratory parameters for: ALT or AST > 5 × ULN, or ALT or AST > 3 × ULN and total bilirubin level > 2 × ULN
•Pregnant
•BMI > 30
•Considered unsuitable by researcher
•FVP (n = 9)
•1600–2200 mg FVP 2 × day 1
•600 mg FVP 3x/day up to 14 days
•Control antivirals
•B/M (n = 10)
•80 mg B/M 1 × day 1,4,7. Day 7 dose for patients with positive test
•Control antivirals
•Control (n = 10)
•100 000 IU IFN-α 3-4x/day
•400/100 mg LPV/r 2x/day
•800/150 mg D/C 1x/day
•200 mg ARB 3x/day
•FVP (n = 9)
•Age, years: 58.0 ± 8.1
•Male: 7 (77.8%)
•WBC, cells/nL: 7.8 (3.9–14.1)
•Time Sx onset to Tx start, days: 8.5 ± 3.7
•B/M (n = 10)
•Age, years: 53.3 ± 12.5
•Male: 7 (70.0%)
•WBC, cells/nL 8.3 (3.3–27.9)
•Time Sx onset to Tx start, days: 12.7 ± 3.5
•Control
•Age, years: 46.6 ± 14.1
•Male: 7 (70.0%)
•WBC, cells/nL: 6.3 (2.9–19.4)
•Time Sx onset to Tx start, days: 13.6 ± 4.6
•No patients excluded from analysis
Shinkai et al. [52] Efficacy and Safety of Favipiravir in Moderate COVID-
19 Pneumonia Patients without Oxygen Therapy:
A Randomized, Phase III Clinical Trial
SBRCT •20–74 years of age
•Positive SARS-CoV-2 based on a nucleic acid amplification test of a respiratory tract sample taken at enrollment
•Pulmonary lesions confirmed by chest imaging
•Fever > 37.5 °C
•Written informed
•consent obtained from the patient
• ≥ 11 days since onset of fever of > 37.5 °C
•Infection episode was a relapse or reinfection
••SpO2 < 94% without oxygen therapy
•FVP (n = 107)
•D1: 1800 mg FVP 2x/day
•D2-D13: 800 mg 2x/day, duration of treatment variable based on patient improvement
•Placebo (n = 49)
•Matching placebo tablets for up to
••14 days
•FVP (n = 107)
•Age, years: 43.8 ± 12.5
•Male: 76 (71.0%)
•SpO2 adm: 96.1 ± 1.7
•Placebo (n = 49)
•Age, years: 48.7 ± 14.1
•Male: 28 (57.1%)
•SpO2 adm: 96.0 ± 2.1
•No patients excluded from analysis
Solaymani-Dodaran et al. [44] Safety and efficacy of Favipiravir in moderate to severe
SARS-CoV-2 pneumonia
OLRCT •16–100 years of age
•Diagnosis of SARS-CoV-2 based on either a positive RT-PCR test or typical ground
•glass appearance on chest CT scan in need of hospital admission due to a SpO2 of ≤ 93%
•Informed and written consent
•History of receiving any antiviral drug (Ribavirin,
•Oseltamivir, and LPV/r) for current illness
•History of
•chronic renal or liver failure, or gastrointestinal bleeding
• < 48 h life expectancy
•Pregnant or lactating females
•Known HIV infection/AIDS
•QT interval > 500 ms in
•ECG
•FVP (n = 190)
•1600 mg FVP immediately
•D1-D7: 600 mg FVP every 8 h + 200 mg HCQ 2x/day
•Daily HCQ reduced to a single dose on D1 after trial started
•LPV/r (n = 183)
•200 mg HCQ on admission
D1-D7: 400 mg/100 mg LPV/r 2x/day
•FVP (n = 190)
•Age, years: 58.6 ± 17.5
•Male: 115 (60.5%)
•SpO2 adm: 89 (5)
•WBC, cells/nL (n = 184): 6.9 (5.1–8.9)
•LPV/r (n = 183)
•Age, years: 56.6 ± 17.1
•Male: 90 (49.2%)
•SpO2 adm: 89 (7)
WBC, cells/nL (n = 169): 6.3 (4.9–9.1)
•FVP
•Randomized: 216
•Included in outcome analysis: 190
•LPV/r
•Randomized: 208
•Included in outcome analysis: 183
Udwadia et al. [35] Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial OLRCT •18–75 years of age
•Patients admitted to the hospital with mild (including asymptomatic) to moderate COVID-19
•Confirmed SARS-CoV-2 virus by RT-PCR within 48 h prior to randomization
•No participation in any other interventional clinical study
•Agreement to use effective contraception during study and for ≥ 7 days following the last treatment
•Negative pretreatment pregnancy test for female patients of child-bearing potential
••Time from symptom onset to randomization no more than 7 days for mild disease and 10 days for moderate disease
•Severe infection
•SpO2 ≤ 93% or PaO2/FiO2 ≤ 300 mmHg
•Current ICU care for the management of ongoing clinical status
•Inability to take or tolerate oral medications
•Allergy or hypersensitivity to favipiravir
•Asthma or chronic obstructive lung disease
•Severe liver disease
•History of gout or hyperuricemia
•Prolonged QT (QTc ≥ 450 ms for men and as QTc ≥ 470 ms for women)
•Severely reduced left ventricular function
•Severe renal impairment or having received continuous renal replacement therapy, hemodialysis or peritoneal dialysis
•Prohibited concomitant medications included: HCQ or CQ, pyrazinamide, repaglinide, theophylline and famciclovir or sulindac
•FVP (n = 72)
•D1: 1800 mg favipiravir 2x/day
•D2-D14: 800 mg favipiravir 2x/day + standard supportive care
•Control (n = 75)
•Supportive care alone
•FVP (n = 72)
•Age, years: 43.6 ± 12.2
•Male: 51 (70.8%)
•Control (n = 75)
•Age, years: 43.0 ± 11.2
•Male: 57 (76.0%)
•FVP
•Randomized: 75
•Included in outcome analysis: 72
•Control
•Randomized: 75
•Included in outcome analysis: 75
Zhao et al. [45] Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial OLRCT • ≥ 18 years of age
•After first diagnosis and treatment of COVID-19, 2 consecutive (24 h apart) negative SARS-CoV-2 RNA tests of sputum or nasopharyngeal swabs
•During screening (follow-up after discharge), a positive SARS-CoV-2 RNA tests of sputum, nasopharyngeal swabs, blood, feces, or other specimen
•Volunteered to participate in the research
•FVP allergy
•Pregnant or lactating
••Patient determined unsuitable for participation
•FVP (n = 36)
•1600 mg 2 × day 1
•600 mg 2 × day 2–7
•As needed after day 7 until day 14
•Control (n = 19)
•Received drugs other than favipiravir and treatment according to the needs of the disease
•FVP
•Age, years: 55.8 ± 14.2
•Male: 16 (44.4%)
•WBC, cells/nL 5.9 ± 1.8
•Control
•Age: 55.5 ± 12.6
•Male: 9 (47.4%)
•WBC, cells/nL 5.7 ± 1.4
•No patients excluded from analysis
•Lopinavir/Ritonavir
Ader et al. [37] An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/
ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with
COVID-19
OLRCT • ≥ 18 years of age
•Laboratory-confirmed SARS-CoV-2 infection by PCR, or other commercial or public health assay in any specimen < 72 h prior to randomization
•Hospitalized patients with illness of any duration, and at least one of the following:
oClinical assessment (evidence of rales/crackles on physical examination) AND SpO2 ≤ 94% on room air, OR
oacute respiratory failure requiring supplemental oxygen, high flow oxygen devices, non-invasive ventilation, and/or mechanical ventilation
•Women of childbearing potential must agree to use contraception for the duration of the study
•Refusal to participate expressed by patient or legally authorized representative if they are present
•Spontaneous blood alanine transferase (ALT)/AST levels > 5 times the upper limit of normal
•Stage 4 severe CKD or requiring dialysis
•Pregnancy or breast-feeding
•Anticipated transfer to another hospital, which is not a study site within 72 h
•Patients previously treated with one of the antivirals evaluated in the trial in the past 29 days
•Contraindication to any study medication including allergy
•Use of medications that are contraindicated with LPV/r and HCQ
•HIV infection under HAART
•History of severe depression or attempted suicide or current suicidal ideation
•cQT interval > 500 ms
•LPV/r (n = 145)
•D1-D14: 400 mg/100 mg LPV/r 2x/day
•SoC
•LPV/r + IFN (n = 145)
•D1-D14: 400 mg/100 mg LPV/r 2x/day
•D1, D3, D6: 44 μg of
•subcutaneous IFN-β-1a
•SoC
•HCQ (n = 145)
•D1: 400 mg HCQ 2x/day
•D2-D9: 400 mg HCQ 1x/day
•SoC
•Control (n = 148)
•SoC
•LPV/r (n = 145)
•Age, years: 63 (55–71)
•Male: 106 (73.1%)
•Time Sx onset to Tx start, days: 10.0 (7.0–13.0)
•LPV/r + IFN (n = 145)
•Age, years: 64 (53–71)
•Male: 103 (71.0%)
•Time Sx onset to Tx start, days: 10.0 (7.0–12.0)
•HCQ (n = 145)
•Age, years: 65 (55–71)
•Male: 104 (71.7%)
•Time Sx onset to Tx start, days: 8.0 (7.0–11.0)
•Control (n = 148)
•Age, years: 62 (52–71)
•Male: 105 (70.9%)
•Time Sx onset to Tx start, days: 9.0 (7.0–12.0)
•Total patients
•Randomized: 603
•Included in outcome analysis: 583
•LPV/r
•Included in outcome analysis: 145
•LPV/r + IFN
•Included in outcome analysis: 145
•HCQ
•Included in outcome analysis: 145
•Control
•Included in outcome analysis: 148
Alavi Darazam et al. [47] Umifenovir in hospitalized moderate to severe COVID-19 patients: A
randomized clinical trial
OLRCT • ≥ 18 years of age
•Presence of at least one of the following manifestation: (radiation contactless body temperature ≥ 37.5 ◦C, cough, shortness of breath, nasal congestion/discharge,
•myalgia/arthralgia, diarrhea/vomiting, headache or fatigue)
•Peripheral capillary SpO2 ≤ 93% on pulse oximetry
•Respiratory frequency ≥ 24/minute while breathing ambient air (on admission day)
•Acute onset of symptoms ≤ 14 days
•Consumption of potentially interacting
•medications with LPV/r or IFN-β-1a
•Pregnancy and
•breastfeeding
•History of alcohol use disorder, or any illicit drug dependence within the past five years
•Blood AST/ALT levels ≥ fivefold higher relative to maximum limit of normal range on laboratory findings
•Participation refusal who needed invasive ventilation from the beginning
•LPV/r + HCQ + IFN-β-1a + ARB (n = 51)
•LPV/r (400 mg/100 mg bid for 10–14
•days) + HCQ (400 mg single dose) + interferon-β1a (Subcutaneous injections of 44 μg (12,000 IU) on days 1, 3, 5) + ARB (200 mg trice daily for 10 days)
•Control (n = 50)
•LPV/r (same dose) + HCQ (same dose) + IFN-β-1a (same dose)
•LPV/r + HCQ + interferon-β-1a + ARB (n = 51)
•Age, years: 62.1 ± 15.3
•Male: 31 (60.8%)
•SpO2: 85 (80–85)
•WBC, cells/nL
• < 4: 8 (18.2%)
•4-10: 33 (75.0%)
• > 10: 3 (6.8%)
•Control (n = 50)
•Age, years: 60.2 ± 16.5
•Male: 26 (52.0%)
•SpO2: 86 (80–88)
•WBC, cells/nL
o < 4: 10 (21.7%)
o4-10: 29 (63.0%)
o > 10: 7 (15.2%)
•No patients excluded from analysis
Arabi et al. [38] Lopinavir-ritonavir and hydroxychloroquine
for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
OLRCT •Adults ≥ 18 years of age
•Admitted with suspected or confirmed COVID-19
•Receiving respiratory or cardiovascular organ failure support
•in an ICU
•In addition to patients enrolled in the COVID-19 Antiviral Therapy
•Domain, the primary model included patients enrolled in other domains in Severe State, for covariate adjustment
•Death deemed to be imminent during the next 24 h AND one or more of the patient, substitute decision-maker, or attending physician are not committed to full active treatment
•Expected discharged from the hospital the same day or the following day
•14 + days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection
•Previous participation in this REMAP-CAP within last 90 days
•Known hypersensitivity to lopinavir-ritonavir and HCQ
•Receiving lopinavir-ritonavir or HCQ as a usual medication prior to this hospitalization
•Known HIV infection
•Severe liver failure
•Known or suspected pregnancy
•Receiving
•amiodarone as a usual medication prior to this hospitalization or any administration of amiodarone within the 72 h prior to the assessment of eligibility
•High clinical risk
•of sustained ventricular dysrhythmia
•LPV/r (n = 225)
•400 mg of lopinavir and 100 mg of ritonavir every 12 h
•Administered for 5 days minimum, up to a maximum of 14 days or until ICU
•discharge whichever occurred first
•HCQ (n = 50)
•Two loading
•doses of 800 mg, 6 h apart, followed 6 h later by 400 mg
•12 hourly for 12 doses
•Combination therapy (n = 27)
•Control (n = 362)
•LPV/r (n = 225)
•Age, years: 61.0 ± 13.0
•Male: 182 (71.7%)
•HCQ (n = 50)
•Age, years: 56.3 ± 13.0
•Male: 35 (70%)
•Combination therapy (n = 27)
•Age, years: 60.3 ± 8.9
•Male: 19 (70.4%)
•Control (n = 362)
•Age, years: 60.8 ± 12.9
•Male: 252 (69.6%)
•LPV/r:
•Randomized: 268
•Included in analysis: 249
•HCQ:
•Randomized: 52
•Included in analysis: 49
•Combination therapy:
•Randomized: 29
•Included in analysis: 26
•Control:
•Randomized: 377
•Included in analysis: 353
Cao et al. [24] A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 OLRCT •Positive RT-PCR
•Male and nonpregnant female patients ≥ 18 years of age
•Pneumonia confirmed by chest imaging
•Sao2 ≤ 94% while breathing ambient air or a ratio of Pao2:Fio2 ≤ 300 mg Hg
•Physician decision that involvement in the trial was not in the patient’s best interest
•Any condition that would not allow the protocol to be followed safely
•Known allergy or hypersensitivity to lopinavir–ritonavir
•Known severe liver disease (e.g., cirrhosis, ALT > 5 × upper limit of the normal range or AST > 5 × upper limit of the normal range)
•Use of medications that are contra-indicated with lopinavir–ritonavir and that could not be replaced or stopped during the trial period
•Pregnancy or breastfeeding
•Known HIV infection
•LPV/r
•D1-D14: 400 mg/100 mg LPV/r 2x/day
•SoC
•Control
•SoC
•LPV/r (n = 99)
•Age, years: 58.0 (50.0, 68.0)
•Male: 61 (61.6%)
•WBC, cells/nL: 7.3 (5.3, 9.6)
•Time Sx onset to Tx start, days: 13 (11, 17)
•Control (n = 100)
•Age, years: 58.0 (48.0, 68.0)
•Male: 59 (59.0%)
•WBC, cells/nL 6.9 (4.9, 9.1)
•Time Sx onset to Tx start, days: 3 (10, 16)
•LPV/r:
•Randomized: 99
•Included in analysis: 96
•Control:
•Randomized: 100
•Included in analysis: 100
Li et al. [29] Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial SBRCT •18–80 years of age
•SARS-CoV-2 confirmed by RT-PCR from pharyngeal swab
•Mild clinical status “defined as having mild clinical symptoms but no signs of pneumonia on imaging” OR moderate clinical status “defined as having fever, respiratory symptoms and pneumonia on imaging”
•Lab findings: (1) creatinine ≤ 110 μmol/L, (2) creatinine clearance rate (eGFR) ≥ 60 ml/min/1.73m2, (3) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN, and (4) total bilirubin (TBIL) ≤ 2 × ULN
•Voluntarily and provided informed consent
•Known or suspected to be allergic to LPV/r or ARB
•Severe nausea, vomiting, diarrhea, or other complaints affecting oral intake or absorption in the digestive tract
•Medications contraindicated with LPV/r or ARB
•Serious underlying diseases (including but not limited to heart, lung, or kidney disease, liver malfunction, or mental illnesses affecting treatment compliance)
•Complications with pancreatitis or hemophilia prior to the trial
•Pregnant or lactating females
•Suspected or confirmed history of alcohol or substance use disorder
•Participation in other drug trials within the past month
•Considered unsuitable by researchers
•LPV/r (n = 34)
•D1-D14: 500 mg/100 mg LPV/r 2x/day
•Minimum 7 days treatment
•ARB (n = 35)
•D1-D14: 200 mg 3x/day
•Minimum 7 days
•Control (n = 17)
•Supportive care only
•LPV/r (n = 34)
•Age, years: 50.7 ± 15.4
•Male: 17 (50.0%)
•WBC, cells/nL
o < 4: 8 (23.5%)
o4-10: 25 (73.5%)
o > 10: 1 (2.9%)
•Time Sx onset to Tx start, days: 3.5 (2, 6)
•ARB (n = 35)
•Age, years: 50.5 ± 14.6
•Male: 16 (45.7%)
•WBC, cells/nL
• < 4: 11 (31.4%)
•4-10: 24 (68.6%)
• > 10: 0 (0.0%)
•Time Sx onset to Tx start, days: 6 (2, 8)
•Control (n = 17)
•Age, years: 44.3 (27–62)
•Male: 7 (41.2%)
•WBC, cells/nL
o < 4: 3 (17.6%)
o4-10: 14 (82.4%)
o > 10: 0 (0.0%)
•Time Sx onset to Tx start, days: 5 (2.8%)
•No patients excluded from analysis
Nojomi et al. [31] Effect of Arbidol (Umifenovir) on COVID-19:
a randomized controlled trial
OLRCT • ≥ 18 years of age
•Hospitalized at study center
•Allergy to ARB class of drugs
•Abnormal liver or renal function
•Abnormal blood coagulation
•Pregnant or nursing
•Severe heart disease
•LPV/r (n = 50)
•D1: 400 mg HCQ 2x/day
•D1 + : 400 mg/100 mg LPV/r 2x/day
•7–14 days depending on disease severity
•ARB (n = 50)
•D1: 400 mg HCQ 2x/day
•D1 + : 200 mg ARB 3x/day
••7–14 days depending on disease severity
•LPV/r (n = 50)
•Age, years: 56.2 ± 14.8
•Male: 27 (54.0%)
•SpO2 adm: 84.3% ± 7.7
•WBC: 9.8 ± 5.5
•ARB (n = 50)
•Age, years: 56.6 ± 17.8
•Male: 33 (66.0%)
•SpO2 adm: 85.5% ± 8.4
••WBC: 10.5 ± 4.1
•No patients excluded from analysis
RECOVERY collaborative group [26] Lopinavir–ritonavir in patients admitted to hospital with COVID-19
(RECOVERY): a randomised, controlled, open-label, platform trial
OLRCT •Admitted patients with clinically suspected or laboratory confirmed SARS-CoV-2 infection
•No medical history that might put the patient at substantial risk if they were to participate in the trial
•Initially, recruitment limited to patients who were ≥ 18 years of age but from May 9, 2020, this age limit was removed
•Written informed consent from all patients or their legal representative
•Patient with severe hepatic insufficiency
••Patients using medicinal products that are highly dependent on cytochrome P450 3A4 for clearance and for whom elevated plasma concentrations would be associated with serious or life-threatening events (in line with the summary of product characteristics)
•LPV/r (n = 1616)
•400 mg/100 mg LPV/r 2x/day
•maximum 10 days or until discharge, if sooner
•Standard care (n = 3424)
•LPV/r (n = 1616)
•Age, years: 66.0 ± 16.0
•Male: 973 (60%)
•Time Sx onset to Tx start, days: 8 (5, 12)
•Standard care (n = 3424)
•Age, years: 66.4 ± 15.8
•Male: 2104 (61%)
••Time Sx onset to Tx start, days: 8 (4, 12)
•No patients excluded from analysis
Reis et al. [27] Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir
on Risk of Hospitalization Among Patients With COVID-19
The TOGETHER Randomized Clinical Trial
DBRCT •Adults ≥ 18 years of age
• < 8 days since onset of flulike symptoms or chest computerized tomography scan consistent with COVID-19
•At least one additional criterion for high risk:
o ≥ 50 years of age
oPresence of pulmonary disease
oDiabetes requiring oral medication or insulin
oHypertension requiring treatment
oKnown cardiovascular diseases
oSymptomatic lung disease on chronic treatment
oHistory of transplantation
oObesity
oImmunocompromised status due to disease
oImmunocompromised status due to medication
oPatients with cancer
•Use of any of study drugs in 30 days prior to screening
•Clinical
•evidence of progression of COVID-19 (i.e., use of oxygen supplementation; arterial oxygen saturation
•less than 94%; use of noninvasive positive-pressure ventilation support)
•History of known life-threatening cardiac arrhythmias
•Long QT syndrome
••Known allergy to study drugs
•LPV/r (n = 244)
•D1: 800 mg/200 mg LPV/r 2x/day
•D2-D10: 400 mg/100 mg LPV/r 2x/day
•HCQ (n = 214)
•D1: 800 mg HCQ
•D2-D10: 400 mg HCQ
•Placebo (n = 227)
•Received corresponding tablets of inert material
•(talc)
•Placebo bottles were matched for the same number of tablets as active HCQ
•(placebo of HCQ) and active LPV/r (placebo of LPV/r)
•LPV/r (n = 244)
•Age, years: 54 (range: 18–94)
•Male: 110 (45.1%)
•Time Sx onset to Tx start, days:
• > 5: 210 (86.1%)
• ≤ 5: 34 (13.9%)
•HCQ (n = 214)
•Age, years: 53 (range: 18–81)
•Male: 92 (43.0%)
•Time Sx onset to Tx start, days:
o > 5: 177 (82.7%)
o ≤ 5: 37 (17.3%)
•Placebo (n = 227)
•Age, years: 53 (range: 18–80)
•Male: 106 (46.7%)
•Time Sx onset to Tx start, days:
o > 5: 187 (82.4%)
o ≤ 5: 40 (17.6%)
•No patients excluded from analysis
Remdesivir
Barratt-Due et al. [39] Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19: A Randomized Trial OLRCT • ≥ 18 years of age
•SARS-CoV-2 infection confirmed by RT-PCR
•Admitted to the hospital ward or ICU with no anticipated transfer to a non-
•study hospital within 72 h of inclusion
•Informed consent
•Severe comorbid conditions with life expectancy less than 3 months
•Level of AST or ALT > 5 × the upper limit of normal
•Rate-corrected QT
•interval greater than 470 ms
•Pregnancy/ breastfeeding
•Acute occurrence of a comorbid condition in a 7-day period before inclusion
•Known intolerance to study drugs
•Participation in a potentially confounding trial, or concomitant medications interfering with the study drugs
RDV (n = 42)
•D1: 200 mg of intravenous RDV
•D2 + : 100 mg RDV up to 9 days
•SoC
RDV control (n = 57)
•SoC
HCQ (n = 52)
•D1: 800 mg of oral
•HCQ 2x/ day 1,
•D2 + : 400 mg 2x/day, up to 9 days
•SoC
HCQ control (n = 54)
•SoC
RDV (n = 42)
•Age, years: 59.7 ± 16.5
•Male: 29 (69.0%)
RDV control (n = 57)
•Age, years: 58.1 ± 15.7
•Male: 43 (75.4%)
HCQ (n = 52)
•Age, years: 60.3 ± 13.3
•Male: 31 (59.6%)
HCQ control (n = 54)
•Age, years: 59.2 ± 16.4
•Male: 34 (63.0%)
RDV:
•Randomized: 43
•Included in analysis: 42
RDV Control:
•Randomized: 58
•Included in analysis: 57
HCQ:
•Randomized: 54
•Included in analysis: 52
HCQ Control:
•Randomized: 54
•Included in analysis: 54
Beigel et al. [23] Remdesivir for the Treatment of Covid-19—Final Report DBRCT • ≥ 18 years of age
•Admitted with symptoms suggestive of COVID-19
•Provides informed consent
•Understands and agrees to comply with planned study procedures
•Not pregnant
•Laboratory-confirmed SARS-CoV-2 infection (RT-PCR positive in sample collected < 72 h prior to randomization; OR RT-PCR positive in sample collected ≥ 72 h prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 h, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection
•Illness of any duration, and at least one of the following: radiographic infiltrates by imaging, OR SpO2 ≤ 94% on room air, OR requiring supplemental oxygen, OR requiring mechanical ventilation
•Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29
•Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29
•ALT or AST > 5 × upper limit of normal
•eGFR < 30 ml/min (including patients receiving hemodialysis or hemofiltration)
•Pregnancy or breast feeding
•Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 h
•Allergy to any study medication
RDV (n = 541)
•D1: 200 mg RDV
•D2-D10: 100 mg RDV
Control (n = 521)
•Equal volume of placebo using same schedule as RDV
RDV (n = 541)
•Age, years: 58.6 ± 14.6
•Male: 352 (65.1%)
•Time Sx onset to Tx start, days: 9 (6, 12)
Control (n = 521)
•Age, years: 59.2 ± 15.4
•Male: 332 (63.7%)
•Time Sx onset to Tx start, days: 9 (7, 13)
RDV:
•Randomized: 541
•Included in analysis: 531
Control:
•Randomized: 521
•Included in analysis: 517
Goldman et al. [53] Remdesivir for 5 or 10 Days in Patients
with Severe Covid-19
OLRCT • ≥ 12 years of age
•Hospitalized
•SARS-CoV-2 infection confirmed by polymerase-chain-reaction assay within 4 days before randomization
•Radiographic evidence of pulmonary infiltrates and either had SpO2 ≤ 94% while breathing ambient air or were receiving supplemental oxygen
•Patients receiving mechanical ventilation and ECMO at screening
•Patients with signs of multiorgan failure
•ALT or AST levels > 5 × upper limit of the normal range or estimated creatinine clearance < 50 ml per minute (by the Cockcroft–Gault formula)
•Patients receiving concurrent treatment (within 24 h before the start of trial treatment) with other agents with putative activity against Covid-19
5-day RDV (n = 200)
•D1: 200 mg RDV
•D2-D5: 100 mg RDV
10-day RDV (n = 197)
•D1: 200 mg RDV
•D2-D9: 100 mg RDV
5-day RDV (n = 200)
•Age, years: 61 (50, 69)
•Male: 120 (60.0%)
•Time Sx onset to Tx start, days: 8 (5, 11)
10-day RDV (n = 197)
•Age, years: 62 (50, 71)
•Male: 133 (67.5%)
•Time Sx onset to Tx start, days: 9 (6, 12)
No patients excluded from analysis
Mahajan et al. [51] Clinical outcomes of using remdesivir in patients with moderate to severe COVID-19: A prospective randomised study OLRCT •18–60 years of age
•Hospitalized
•SARS-CoV-2 infection confirmed by RT-PCR within the last 4 days
•Radiographic evidence of pneumonia
•Respiratory rate > 24/min
•Oxygen saturation of ≤ 94%
•Creatinine clearance > 40 ml per minute
•Patients receiving mechanical ventilation
•Patients with multi organ failure
•ALT and AST levels greater than 3 × ULN
RDV + SoC (n = 34)
•D1: 200 mg RDV
•D2-D5: 100 mg RDV
SoC (n = 36)
RDV + SoC (n = 34)
•Age, years: 58.1 ± 12.1
•Male: 21 (61.7%)
•Time Sx onset to Tx start, days: 6.26 ± 2.49
SoC (n = 36)
•Age, years: 57.4 ± 14.1
•Male: 27 (75.0%)
•Time Sx onset to Tx start, days: 7.38 ± 0.99
RDV + SoC:
•Randomized: 41
•Included in analysis: 34
SoC:
•Randomized: 41
•Moved to RDV: 1
•Included in analysis: 36
Spinner et al. [34] Effects of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19 A Randomized Clinical Trial OLRCT • ≥ 12 years of age
•Written informed consent (participants ≥ 18 years of age)
•Assent and written informed consent from a parent/legal guardian (participants ≥ 12 and < 18 years of age)
•Hospitalized
•SARS-CoV-2 infection confirmed by RT-PCR assay ≤ 4 days before randomization
•Moderate COVID-19 pneumonia (defined as any radiographic evidence of pulmonary infiltrates and SpO2 > 94% on room air)
•Participation in any other clinical trial of an experimental agent treatment for COVID-19
•Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 h prior to study
•Requiring mechanical ventilation at screening
•ALT or AST > 5 times the upper limit of normal
•Creatinine clearance < 50 mL/min
•Positive pregnancy test
•Breastfeeding
•Known hypersensitivity to the study drug, the metabolites, or formulation excipient
5-day RDV (n = 191)
•D1: 200 mg RDV
•D2-D5: 100 mg RDV
10-day RDV (n = 193)
•D1: 200 mg RDV
•D2-D10: 100 mg RDV
Standard care (n = 200)
5-Day RDV (n = 191)
•Age, years: 58 (48, 66)
•Male: 114 (59.7%)
10-Day RDV (n = 193)
•Age, years: 56 (45, 66)
•Male: 118 (61.1%)
Standard care (n = 200)
•Age, years: 57 (45, 66)
•Male: 125 (62.5%)
5-day RDV:
•Randomized: 199
•Included in analysis: 191
10-day RDV:
•Randomized: 197
•Included in analysis: 193
Control:
•Randomized: 200
•Included in analysis: 200
Wang et al. [36] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial DBRCT • ≥ 18 years of age
•RT-PCR positive for SARS-CoV-2
•Pneumonia confirmed by chest imaging
•SpO2 ≤ 94% on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of ≤ 300 mm Hg
•Within 12 days of symptom onset
•Eligible patients of child-bearing age (men and women) agreed to take effective contraceptive measures (including hormonal contraception, barrier methods, or abstinence) during the study period and for at least 7 days after the last study drug administration
•Pregnancy or breast feeding
•Hepatic cirrhosis
•ALT or AST > 5 × ULN
•Known severe renal impairment (eGFR < 30 mL/min per 1·73 m2) or receipt of continuous renal replacement therapy
•Hemodialysis or peritoneal dialysis
•Possibility of transfer to a non-study hospital within 72 h
•Enrollment into an investigational treatment study for COVID-19 in the 30 days before screening
RDV (n = 158)
•D1: 200 mg RDV
•D2-D10: 100 mg RDV
Control (n = 78)
•Equal volume of placebo using same schedule as RDV
RDV (n = 158)
•Age, years: 60.0 (57.0, 73.0)
•Male: 89 (56%)
•WBC, cells/nL 6.2 (4.4, 8.3)
•Time Sx onset to Tx start, days: 11 (9, 12)
Control (n = 78)
•Age, years: 64.0 (53.0, 70.0)
•Male: 51 (65%)
•WBC, cells/nL 6.4 (4.5, 8.3)
Time Sx onset to Tx start, days: 10 (9, 12)
RDV:
•Randomized: 158
•Included in analysis: 158
Control:
•Randomized: 79
•Included in analysis: 78
Sofosbuvir
Abbaspour-Kasgari et al. [22] Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial OLRCT •18–80 years of age
•Positive qualitative RT–PCR for SARS-CoV-2 and/or features consistent with COVID-19 on a chest CT scan was required
•Moderate disease on admission were included, which was defined as respiratory rate of < 24/min, arterial O2 saturation of > 94% and symptom onset ≤ 8 days prior to admission, together with compatible findings in a chest CT scan
•Written informed consent
•Patients with multiorgan failure, active cancer, renal insufficiency (creatine clearance less than 50 mL/min/1.73 m2), anemia (hemoglobin less than 9 g/dL)
•Pregnant women or men with a pregnant spouse
•Patients treated with amiodarone, phenytoin, phenobarbital, rifabutin or carbamazepine
SOF/DCV + ribavirin (n = 24)
•400 mg/60 mg SOF/DCV
•1200 mg ribavirin
Standard care (n = 24)
•400 mg HCQ
•400/100 mg LPV/r, 2x/day
•1200 mg ribavirin at physician’s discretion
SOF/DCV + ribavirin (n = 24)
•Age, years: 45.0 (38.0, 69.0)
•Male: 11 (45.8%)
•WBC, cells/nL: 6.4 (5.2, 7.7)
Standard care (n = 24)
•Age, years: 60 (47.5, 68.5)
•Male: 7 (29.2%)
•WBC, cells/nL: 6.2 (5.9, 9.2)
No patients excluded from analysis
Abbass et al. [46] Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir
in patients with COVID‐19: A randomized controlled trial
OLRCT • ≥ 18 years of age
•Laboratory‐confirmed symptomatic COVID‐19 determined by PCR assay in any specimen collected < 72 h before randomization
•Willing and able to provide written
•informed consent
•Had the following disease severity grades: moderate (patients with respiratory rate ≥ 20 breaths/min, oxygen saturation
•measured through a pulse oximeter [SpO2]˃90% on room air and heart
•rate ≥ 90 beats/min), severe (not critical) (patients with clinical signs indicative of severe systematic illness with COVID‐19; such as respiratory
•rate ≥ 30/min, heart rate ≥ 125/min, SpO2 ≤ 90% on room air or PaO2/
•FiO2 < 300
•Critically severe COVID‐19 requiring invasive mechanical ventilation at screening
•Severe concomitant illness
•Hypersensitivity or contraindication to any of the drugs used in the study
•Liver cirrhosis or elevated ALT, and/or AST above 3 × ULN
•Cardiac ischemia or clinically symptomatic cardiac abnormalities
•History of any malignancy
•within the last 5 years
•History of solid organ or bone
•marrow transplantation
•Received treatment with any other investigational drug/device or involved in another clinical trial
•within 6 months before screening
•HIV
•Pregnant or breastfeeding
SOF/DCV + SoC (n = 40)
•D1-D10: 400 mg/60 mg SOF/DCV
•SoC
SOF/ravidasvir + SoC (n = 40)
•D1-D10: 400 mg/200 mg SOF/ravidasvir
•SoC
SoC (n = 40)
SOF/DCV + SoC (n = 40)
•Age, years: 40.0 ± 6.1
•Male: 22 (55.0%)
•SpO2 adm: 88.5% ± 5.6
SOF/RDV + SoC (n = 40)
•Age, years: 48.0 ± 2.2
•Male: 22 (55.0%)
•SpO2 adm: 87.8% ± 4.9
SoC (n = 40)
•Age, years: 46.0 ± 5.8
•Male: 20 (50.0%)
•SpO2 adm: 88.7% ± 4.9
No patients excluded from analysis
El-Bendary et al. [49] Efficacy of combined Sofosbuvir and Daclatasvir
in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study
OLRCT • ≥ 18 years of age
•Not pregnant
•Positive RT-PCR test for
•SARS-CoV-2 on nasopharyngeal swab
•Evidence of pneumonia on CT chest imaging
•Known allergy
•or hypersensitivity to the used medications
•Known seizure
•disorder
•Presence of either active HCV or severe liver disease
•(e.g. cirrhosis, elevated liver transaminases > 5 × the upper limit
•of the normal range)
•Pregnancy or breast-feeding
•Cases with history of bone marrow transplant
•Glucose 6 phosphate dehydrogenase deficiency
•End stage renal disease, psoriasis, porphyria and patients with a known history of long QT syndrome
•or current known QTc > 500 ms
SOF/DCV (n = 96)
•D1-D14: 400 mg/60 mg SOF/DCV
•In combination with the conventional
•therapy that included HCQ (400 mg twice daily for 1 day, then 200 mg twice daily for 14 days)
Control (n = 78)
•Conventional
•therapy including HCQ without SOF/DCV
SOF/DCV (n = 96)
•Age, years: 52 (37, 67)
•Male: 53 (55.2%)
•SpO2 adm: 89.69% ± 6.54
Control (n = 78)
•Age, years: 54 (39, 69)
•Male: 42 (53.8%)
•SpO2 adm: 91.0% ± 5.0
No patients excluded from analysis
Khalili et al. [28] Efficacy and safety of sofosbuvir/ ledipasvir in treatment of
patients with COVID-19; A randomized clinical trial
OLRCT • ≥ 18 years of age
•Admitted to the hospital
•Highly suspected (clinical signs/symptoms & imaging findings) or confirmed (positive PCR pharyngeal or nasopharyngeal samples) COVID-19
•History of drug allergy
•Decompensated cirrhosis
•Severe COVID-19
•Hemodialysis
•Pregnant or lactating
SOF/LDP (n = 42)
•D1-D10: 400 mg/100 mg SOF/LDP
•SoC
Control (n = 40)
•D1-D10: SoC alone
SoC included
•D1: HCQ 400 mg 2x/day
•D2-D7: HCQ: 200 mg 2x/day
•D1-D7: 300 mg/100 mg atazanavir/ritonavir
SOF/LDP (n = 42)
•Age, years: 61.5 (46.5, 74.25)
•SpO2 adm: 90% (88, 93)
•WBC, cells/nL: 6.2 (4.7, 8.4)
•Time Sx onset to Tx start, days: 7 (3.75, 10)
Control (n = 40)
SOF/LDP (n = 42)
•Age, years: 63 (53.25, 70.75)
•SpO2 adm: 90 (88–93.75)
•WBC, cells/nL 5.5 (4.8, 7.5)
•Time Sx onset to Tx start, days: 7 (4, 10)
SOF/LDP:
•Randomized: 45
•Included in analysis: 42
Standard care:
•Randomized: 45
•Included in analysis: 40
Roozbeh et al. [32] Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial DBRCT • ≥ 18 years of age
•Confirmed CT scan findings for COVID-19
•COVID-19 clinical symptoms including fever, cough and fatigue, and positive CRP test
•Written informed consent
•SpO2 ≤ 93%
•Pregnancy
•Amiodarone use
•Renal failure
•Cardiovascular diseases
SOF/DCV + standard care (n = 27)
•D1-D7: 400 mg/60 mg SOF/DCV 2x/day
Standard care (n = 28)
•D1-D7: 200 mg HCQ 2x/day
•D1-D6: 500 mg azithromycin
•D1-D7: 500 mg naproxen, 2x/day
•40 mg pantoprazole tablets
SOF/DCV + standard care (n = 27)
•Age, years: 43 (37, 52)
•Male: 12 (44.4%)
•SpO2 (adm): 98% (97, 98)
Standard care (n = 28)
•Age, years: 47.5 (37, 53)
•Male: 14 (50.0%)
SpO2: 98% (97, 99)
No patients excluded from analysis
Sadeghi et al. [33] Sofosbuvir and daclatasvir compared with SoC in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial OLRCT • ≥ 18 years of age
•Positive RT–PCR nasopharyngeal swab and chest CT scan compatible with moderate or severe COVID-19 infection
•Signs of severity of disease defined as fever (oral temperature ≥ 37.8
•°C at any one time prior to enrolment) and at least one of respiratory rate > 24/min, SpO2 < 94%, or PaO2/FiO2ratio < 300 mgHg
•Onset of symptoms ≤ 8 days
•Written informed consent
•Known allergic reaction to the intervention drugs
•Pregnant or breastfeeding
•Any prior experimental treatment for COVID-19
•HR < 60 bpm
•Taking amiodarone
•Evidence of multiorgan failure
•Requiring invasive mechanical ventilation at screening
•eGFR < 50 mL/1.73 m2/min
SOF/ DCV + standard care (n = 33)
•D1-D14: 400 mg/60 mg SOF/DCV
•Standard care
Standard care (n = 33)
•D1-D14: 200 mg HCQ 2x/day
•With or without 200 mg/50 mg LPV/r 2x/day
SOF/DCV + standard care (n = 33)
•Age, years: 58 (38–65)
•Male: 20 (61%)
•SpO2 (adm): 91 (89, 92)
•WBC, cells/nL: 6.9 (5.6–12.3)
Standard care (n = 33)
•Age, years: 62 (49, 70)
•Male: 14 (42%)
•SpO2 (adm): 90 (88, 92)
•WBC, cells/nL: 10 (6, 12)
No patients excluded from analysis
Sayad et al. [43] Efficacy and safety of sofosbuvir/velpatasvir versus the standard of
care in adults hospitalized with COVID-19: a single-centre, randomized
controlled trial
OLRCT • ≥ 18 years of age
•Positive RT-PCR test for SARS-CoV-2 on a nasopharyngeal swab and/or a compatible chest CT scan
•SpO2 ≤ 93% on ambient air and/or an absolute lymphocyte count of < 1.1 cells/nL
•Pregnancy and breastfeeding
•Physician’s decision against enrollment
•Conditions that did not allow complete implementation of the protocol
•Allergy or hypersensitivity to the drugs used
•Severe liver disease (cirrhosis or ALT or AST level > 5 × the upper limit of the normal range)
•Use of medications that are contraindicated with the drugs used in this trial
•Known HIV infection
•Known HCV infection
•SOF/VEL (n = 40)
•D1-D10: 400 mg/100 mg SOF/VEL
•National SoC
•Control (n = 40)
•National SoC
•National SoC included:
•D1: 400 mg HCQ
•D1-D10: 400 mg/100 mg LPV/r 2x/day
•As needed: supplemental oxygen, non-invasive and invasive ventilation, antimicrobials, vasopressors and corticosteroids
•SOF/VEL (n = 40)
•Age, years: 53.6 ± 16.3
•Male: 20 (50%)
•WBC, cells/nL 5.7 (4.1, 8.6)
•Control: (n = 40)
•Age, years: 54.6 ± 19.4
•Male: 24 (60.0%)
•WBC, cells/nL 7.5 (6.5, 12)
•SOF/VEL:
•Randomized: 40
•Died before treatment: 1
•Control:
•Randomized: 40
•Moved to SOF/VEL: 3
Enisamium
Holubovska1 et al. [50] Enisamium is an inhibitor of the SARS-CoV-2 RNA polymerase and shows improvement of recovery in COVID-19 patients in an interim analysis of a clinical trial DBRCT • ≥ 18 years of age
•Hospitalized patients with moderate severity of COVID-19 infection diagnosed based on a body temperature of ≥ 37.8 °C and laboratory confirmed presence of SARS-CoV-2 RNA by RT-PCR in pharyngeal swabs or sputum
•Informed consent prior to study participation
None reported Total patients: 373, randomized 1:1
Enisamium (n =  ~ 186)
•D1-D7: 500 mg enisamium iodide 4x/day
Placebo (n =  ~ 186)
••D1-D7: 500 mg matching placebo on same schedule
Not reported No patients excluded from analysis
  1. Data are presented as mean ± standard deviation, median (IQR), or n (%) unless otherwise stated
  2. * statistically different from comparator
  3. AIDS = autoimmune deficiency syndrome; ALT = alanine aminotransferase; ARB = umifenovir (Arbidol); AST = aspartate aminotransferase; B/M = baloxavir/marboxil; BMI = body mass index; CKD = chronic kidney disease; CQ; chloroquine; CT = computed tomography; D# = day #; DB = double-blind; D/C = darunavir/cobicistat; DCV = daclatasvir; ECG = electrocardiogram; ECMO = extracorporeal membrane oxygenation; eGFR = estimated glomerular filtration rate; FVP = favipiravir; HAART = highly active antiretroviral therapy; HCQ = hydroxychloroquine; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IFN = interferon; IU = international units; LDP = ledipasvir; LPV/r = lopinavir/ritonavir; OL = open-label; PaO2/FiO2 = arterial partial pressure of oxygen/fraction of inspired oxygen ratio; QTc = corrected QT interval; RDV = Remdesivir; RCT = randomized controlled trial; RT-PCR = reverse transcriptase polymerase chain reaction; SaO2 = arterial oxygen saturation; SoC = standard of care; SOF = sofosbuvir; SpO2 = oxygen saturation; Sx = symptom; Tx = treatment; ULN = upper limit of normal; VEL = velpatasvir; WBC = white blood cells