LitCovid-sentences  

PMC:7195088 / 3587-35170 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T25 0-226 Sentence denotes Members of a panel of 17 experts from the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) were selected; they developed a list of 8 practical therapeutic questions to be addressed.
T26 227-526 Sentence denotes The members of the panel (which included infectious diseases specialists and pneumonologists) were divided into small groups and asked to summarize the available literature and their frontline-based opinion in brief (500 words maximum) narrative answers, plus a conclusive statement for each answer.
T27 527-647 Sentence denotes All the answers and statements were ultimately reviewed and discussed by the entire panel until a consensus was reached.
T28 648-728 Sentence denotes A brief summary of questions and conclusive statements is available in Table 1 .
T29 729-904 Sentence denotes Table 2 summarizes available or ongoing randomized controlled trial (RCT) information for off-label/compassionate-use drugs mostly used for the treatment of COVID-19 patients.
T30 905-1135 Sentence denotes Of note, we focused on pneumologic and anti-infective/anti-inflammatory treatments; the discussion of the therapeutic approach to COVID-19–related cardiovascular/coagulative disorders is outside the scope of this narrative review.
T31 1136-1179 Sentence denotes Table 1 Summary of questions and statements
T32 1180-1198 Sentence denotes Question Statement
T33 1199-1210 Sentence denotes Question 1.
T34 1211-1310 Sentence denotes How to use at best oxygen therapy and noninvasive mechanical ventilation for preventing intubation?
T35 1311-1505 Sentence denotes Supplementary oxygen should be administered to patients with hypoxic respiratory failure for avoiding values of Spo2 lower than 90% and it should be aimed at reaching values not higher than 96%.
T36 1506-1810 Sentence denotes Although still without firm evidence, we currently support the use of CPAP helmet (with gentle ventilation and a PEEP of no more than 10–12 cm of water) if the patient does not respond to standard/HFNC oxygen supplementation and there is no urgent indication for endotracheal intubation (expert opinion).
T37 1811-1893 Sentence denotes However, no clear indications/criteria can be provided pending further experience.
T38 1894-2129 Sentence denotes Finally, it should be kept in mind that patients with COVID-19 can get worse in a few hours, so they should be carefully monitored for worsening respiratory function for rapidly prompting tracheal intubation and mechanical ventilation.
T39 2130-2141 Sentence denotes Question 2.
T40 2142-2182 Sentence denotes Should antiviral agents be administered?
T41 2183-2313 Sentence denotes At the present time, evidence from the first published RCT does not support off-label treatment with LPV/RTV in COVID-19 patients.
T42 2314-2458 Sentence denotes This result should also discourage the use of other protease inhibitors (e.g. darunavir), at least until results of dedicated RCT are available.
T43 2459-2681 Sentence denotes Although promising in preclinical studies, remdesivir should be currently provided to COVID-19 patients only within RCT (preferentially) or compassionate-use/expanded-access programmes, owing to its investigational nature.
T44 2682-2866 Sentence denotes Pending high-level supporting evidence, favipiravir and umifenovir should not be provided an outside RCT, at least in those countries where they are not approved for other indications.
T45 2867-2974 Sentence denotes Oseltamivir or zanamivir should be provided only in the presence of suspected/proven concomitant influenza.
T46 2975-2986 Sentence denotes Question 3.
T47 2987-3041 Sentence denotes Should chloroquine/hydroxychloroquine be administered?
T48 3042-3291 Sentence denotes Pending results of RCT, the use of hydroxychloroquine may be considered for treating worsening patients with COVID-19 only if no important drug interactions can be anticipated and with close monitoring of hepatic, renal function and QT prolongation.
T49 3292-3501 Sentence denotes This is based on its activity in vitro against SARS-CoV-2 (although weak) and on the availability of low-level clinical evidence of anticipation of virus clearance from a small controlled, nonrandomized study.
T50 3502-3674 Sentence denotes However, it should also be kept in mind that the study was highly susceptible to bias and there are still no data regarding hard clinical endpoints such as crude mortality.
T51 3675-3799 Sentence denotes For these reasons, hydroxychloroquine should be preferentially administered within the framework of investigational studies.
T52 3800-3909 Sentence denotes When this is unfeasible, off-label use may be considered according to local protocols and consent procedures.
T53 3910-4106 Sentence denotes In view of the absence of evidence, we are currently unable to support the use of hydroxychloroquine in asymptomatic or mildly symptomatic nonhospitalized patients outside investigational studies.
T54 4107-4144 Sentence denotes The same applies to prophylactic use.
T55 4145-4156 Sentence denotes Question 4.
T56 4157-4192 Sentence denotes Should antibiotics be administered?
T57 4193-4375 Sentence denotes In our opinion, it might be prudent to consider empiric antibiotic treatment in critically ill patients with pneumonia due to COVID-19 in whom bacterial infection cannot be excluded.
T58 4376-4613 Sentence denotes This suggestion is based on the fact that bacterial coinfection (a) is common in patients with viral pneumonia and (b) can be associated with a substantial risk of delaying appropriate treatment, thereby potentially increasing mortality.
T59 4614-4861 Sentence denotes Because of the limited available data on both the microbiologic epidemiology (and the prevalence of antimicrobial resistance) of bacterial superinfections in COVID-19 patients, it is difficult to provide specific pathogen-oriented recommendations.
T60 4862-5276 Sentence denotes Therefore, pending further studies, we suggest to empirically treat COVID-19 patients according to their clinical syndrome (e.g. community-acquired pneumonia, hospital-acquired pneumonia), choosing the best antimicrobial agent or agents on the basis of local guidelines and local antibiotic susceptibility patterns, with early de-escalation or discontinuation according to microbiology results, whenever available.
T61 5277-5288 Sentence denotes Question 5.
T62 5289-5321 Sentence denotes Should steroids be administered?
T63 5322-5475 Sentence denotes So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection.
T64 5476-5619 Sentence denotes As the WHO underlines, there is an important need for efficacy data from RCT for supporting corticosteroid therapy in patients with SARS-Cov-2.
T65 5620-6066 Sentence denotes However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for rapidly progressive pneumonia and clinical deterioration in COVID-19 patients, we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission).
T66 6067-6299 Sentence denotes Yet in the absence of convincing evidence, the following cannot currently be supported: (1) steroid administration stratified according to inflammatory markers; and (b) steroid administration in non–critically ill COVID-19 patients.
T67 6300-6311 Sentence denotes Question 6.
T68 6312-6393 Sentence denotes Should other immunosuppressive and/or immunomodulatory therapies be administered?
T69 6394-6548 Sentence denotes Owing to the lack of high-level evidence, administration of tocilizumab to patients with COVID-19 should preferentially occur within the framework of RCT.
T70 6549-6875 Sentence denotes Off-label use according to local protocols and consent procedures may be considered only in those COVID-19 patients excluded from RCT (or hospitalized where RCT are not available or still to be implemented) and who are worsening while receiving standard supportive care (in the absence of concomitant/superimposed infections).
T71 6876-7345 Sentence denotes In our opinion, this could be a reasonable off-label use of tocilizumab in these early phases of the COVID-19 pandemic, although patients and physicians should be aware that currently there is only a non–peer-reviewed, noncomparative, observational experience (very low evidence from an unreviewed cases series) and that it only supports a potential favourable effect on inflammatory signs and symptoms, while there is no information on any possible effect on survival.
T72 7346-7551 Sentence denotes In the absence of clinical studies, we suggest to preferentially administer also other immunosuppressive and/or immunomodulatory therapies (e.g. anakinra, Janus kinase family enzyme inhibitors) within RCT.
T73 7552-7870 Sentence denotes This also applies to modifications of the immune response through high-dose intravenous immunoglobulins or plasma from convalescent patients, which, although promising in small case series, both deserve dedicated RCT investigation to clearly understand their role in impacting COVID-19 outcomes and their tolerability.
T74 7871-7882 Sentence denotes Question 7.
T75 7883-7934 Sentence denotes What is the optimal timing of treatment initiation?
T76 7935-8230 Sentence denotes Supportive therapy (symptomatic therapy, rehydration and oxygen supplementation, if necessary), should be initiated as soon as the patient manifests respiratory or systemic symptoms, including severe asthenia, high fever, persistent cough and/or clinical or radiologic signs of lung involvement.
T77 8231-8501 Sentence denotes Pending further evidence, in our opinion, antiviral treatments should not be provided to patients with SARS-CoV-2 infection outside RCT or compassionate-use programmes (with the exception of early oseltamivir initiation in patients with suspected concomitant influenza).
T78 8502-8773 Sentence denotes Corticosteroids should be provided early in well-defined categories of patients (patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections), while their role in other COVID-19 patients still remains uncertain.
T79 8774-9160 Sentence denotes Although based on low-level evidence and pending RCT results, in our opinion, early hydroxychloroquine administration may be considered in COVID-19 patients manifesting moderate to severe symptoms, whereas further data are needed to better delineate the true balance between possible favourable effects and toxicity of hydroxychloroquine in mildly symptomatic and asymptomatic patients.
T80 9161-9172 Sentence denotes Question 8.
T81 9173-9212 Sentence denotes What is the optimal treatment duration?
T82 9213-9512 Sentence denotes Chloroquine/hydroxychloroquine treatment should be continued for at least 5 days, and possibly up to 20 days, according to some expert opinions, although it should be noted that data regarding the relative safety of different lengths of administration in COVID-19 patients are currently unavailable.
T83 9513-9640 Sentence denotes Early discontinuation should be considered in the presence of adverse effects (e.g. QT prolongation or hepatic/renal toxicity).
T84 9641-9918 Sentence denotes If the administration of remdesivir is approved within compassionate-use/expanded-access programmes, treatment duration should follow compassionate or expanded access protocols (e.g. up to 10 days according to the most recent compassionate protocol at the time of this review).
T85 9919-10036 Sentence denotes If corticosteroids are provided, we suggest a total treatment duration of 7–10 days, with progressive dose reduction.
T86 10037-10307 Sentence denotes If the patient's condition deteriorates with worsening lung physiology after withdrawal of steroid treatment in the absence of bacterial or fungal superinfection, a second course of corticosteroid treatment may be considered, followed by slow tapering after improvement.
T87 10308-10683 Sentence denotes ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; CPAP, continuous positive airway pressure; HFNC, high-flow nasal cannula; ICU, intensive care unit; LPV/RTV, lopinavir/ritonavir; PEEP, positive end expiratory pressure; RCT, randomized controlled trial; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WHO, World Health Organization.
T88 10684-10859 Sentence denotes Table 2 Available and ongoing RCT on anti-infective and anti-inflammatory drugs most provided as off-label/compassionate treatments in the first phase of the COVID-19 pandemic
T89 10860-11011 Sentence denotes Drug Class/mechanism Published RCT Ongoing RCT for treatment/prevention of COVID-19 (recruiting or not yet recruiting) registered at ClinicalTrials.gov
T90 11012-11078 Sentence denotes Lopinavir/ritonavir Lopinavir is an HIV type 1 protease inhibitor.
T91 11079-11271 Sentence denotes 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.
T92 11272-11349 Sentence denotes Lopinavir/ritonavir was administered at the dosage of 400/100 mg for 14 days.
T93 11350-11429 Sentence denotes The primary time-to-event endpoint was clinical improvement from randomization.
T94 11430-11818 Sentence denotes 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).
T95 11819-11972 Sentence denotes 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.
T96 11973-12145 Sentence denotes 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.
T97 12146-12187 Sentence denotes Open-label RCT (NCT04307693, recruiting).
T98 12188-12247 Sentence denotes Primary endpoint: virus load at day 3, 5, 7, 10, 14 and 18.
T99 12248-12351 Sentence denotes • Comparison of ASC09/ritonavir vs. lopinavir/ritonavir in patients with confirmed COVID-19 pneumoniae.
T100 12352-12401 Sentence denotes Open-label RCT (NCT04261907, not yet recruiting).
T101 12402-12571 Sentence denotes 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).
T102 12572-12674 Sentence denotes • Comparison of lopinavir/ritonavir vs. lopinavir/ritonavir plus umifenovir in patients with COVID-19.
T103 12675-12716 Sentence denotes Open-label RCT (NCT04252885, recruiting).
T104 12717-12793 Sentence denotes Primary endpoint: rate of virus inhibition at day 0, 2, 4, 7, 10, 14 and 21.
T105 12794-12919 Sentence denotes • Comparison of lopinavir/ritonavir vs. lopinavir/ritonavir plus ribavirin plus interferon beta 1b in patients with COVID-19.
T106 12920-12961 Sentence denotes Open-label RCT (NCT04276688, recruiting).
T107 12962-13044 Sentence denotes Primary endpoint: time to negative nasopharyngeal swab RT-PCR (follow-up 30 days).
T108 13045-13188 Sentence denotes • Comparison of only supportive treatment vs. lopinavir/ritonavir vs. oseltamivir vs. umifenovir in patients with confirmed COVID-19 pneumonia.
T109 13189-13230 Sentence denotes Open-label RCT (NCT04255017, recruiting).
T110 13231-13506 Sentence denotes 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.
T111 13507-13619 Sentence denotes • Comparison of chemoprophylaxis with lopinavir/ritonavir vs. placebo in healthcare workers exposed to COVID-19.
T112 13620-13671 Sentence denotes Double-blind RCT (NCT04328285, not yet recruiting).
T113 13672-13766 Sentence denotes Primary endpoint: occurrence of a symptomatic or asymptomatic COVID-19 (follow-up 2.5 months).
T114 13767-13883 Sentence denotes • Comparison of carrimycin vs. lopinavir/ritonavir or umifenovir or chloroquine in patients with COVID-19 pneumonia.
T115 13884-13933 Sentence denotes Open-label RCT (NCT04286503, not yet recruiting).
T116 13934-14116 Sentence denotes 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.
T117 14117-14299 Sentence denotes • 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.
T118 14300-14349 Sentence denotes Open-label RCT (NCT04295551, not yet recruiting).
T119 14350-14411 Sentence denotes Primary endpoint: clinical recovery time (follow-up 28 days).
T120 14412-14581 Sentence denotes • Comparison of lopinavir/ritonavir plus inhaled interferon alfa vs. lopinavir/ritonavir plus inhaled interferon alfa plus xiyanping injection in patients with COVID-19.
T121 14582-14631 Sentence denotes Open-label RCT (NCT04275388, not yet recruiting).
T122 14632-14693 Sentence denotes Primary endpoint: clinical recovery time (follow-up 14 days).
T123 14694-14873 Sentence denotes • Comparison of lopinavir/ritonavir plus inhaled interferon alfa vs. lopinavir/ritonavir plus inhaled interferon alfa plus traditional Chinese medicines in patients with COVID-19.
T124 14874-14915 Sentence denotes Open-label RCT (NCT04251871, recruiting).
T125 14916-14993 Sentence denotes Primary endpoint: time to complete remission of symptoms (follow-up 28 days).
T126 14994-15209 Sentence denotes • 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.
T127 15210-15263 Sentence denotes Partly blinded RCT (NCT04331470, not yet recruiting).
T128 15264-15345 Sentence denotes Primary endpoint: (a) clear CT scan at 3–7 days; (b) negative RT-PCR at 3–7 days.
T129 15346-15457 Sentence denotes • Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. losartan vs. placebos in patients with COVID-19.
T130 15458-15519 Sentence denotes Double-blind, adaptive RCT (NCT04328012, not yet recruiting).
T131 15520-15596 Sentence denotes Primary endpoint: NIAID COVID-19 ordinal severity scale (follow-up 60 days).
T132 15597-15766 Sentence denotes • Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. lopinavir/ritonavir plus interferon beta 1a vs. remdesivir vs. standard of care in patients with COVID-19.
T133 15767-15820 Sentence denotes Double-blind, adaptive RCT (NCT04315948, recruiting).
T134 15821-15892 Sentence denotes Primary endpoint: severity rating on a 7-point ordinal scale at day 15.
T135 15893-16192 Sentence denotes • 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.
T136 16193-16244 Sentence denotes Single-blind RCT (NCT04323345, not yet recruiting).
T137 16245-16438 Sentence denotes 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).
T138 16439-16576 Sentence denotes • Comparison of colchicine (with or without lopinavir/ritonavir) vs. local standard of care in patients with moderate to severe COVID-19.
T139 16577-16626 Sentence denotes Open-label RCT (NCT04328480, not yet recruiting).
T140 16627-16685 Sentence denotes Primary endpoint: all-cause mortality (follow-up 30 days).
T141 16686-17090 Sentence denotes • 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.
T142 17091-17140 Sentence denotes Open-label RCT (NCT04303299, not yet recruiting).
T143 17141-17208 Sentence denotes Primary endpoint: SARS-CoV-2 eradication time (follow-up 24 weeks).
T144 17209-17239 Sentence denotes Remdesivir Adenosine analogue.
T145 17240-17405 Sentence denotes It binds to RNA-dependent RNA polymerase and acts as an RNA-chain terminator • Not available • Comparison of remdesivir vs. placebo in patients with severe COVID-19.
T146 17406-17449 Sentence denotes Double-blind RCT (NCT04257656, recruiting).
T147 17450-17539 Sentence denotes Primary endpoint: clinical status, assessed by an ordinal scale at days 7, 14, 21 and 28.
T148 17540-17622 Sentence denotes • Comparison of remdesivir vs. placebo in patients with mild to moderate COVID-19.
T149 17623-17666 Sentence denotes Double-blind RCT (NCT04252664, recruiting).
T150 17667-17740 Sentence denotes Primary endpoint: time to clinical recovery in hours (follow-up 28 days).
T151 17741-17828 Sentence denotes • Comparison of remdesivir vs. local standard of care in patients with severe COVID-19.
T152 17829-17870 Sentence denotes Open-label RCT (NCT04252664, recruiting).
T153 17871-17978 Sentence denotes Primary endpoint: composite of fever normalization and oxygen saturation normalization (follow-up 14 days).
T154 17979-18068 Sentence denotes • Comparison of remdesivir vs. local standard of care in patients with moderate COVID-19.
T155 18069-18110 Sentence denotes Open-label RCT (NCT04292730, recruiting).
T156 18111-18157 Sentence denotes Primary endpoint: discharged status at day 14.
T157 18158-18223 Sentence denotes • Comparison of remdesivir vs. placebo in patients with COVID-19.
T158 18224-18267 Sentence denotes Double-blind RCT (NCT04280705, recruiting).
T159 18268-18339 Sentence denotes Primary endpoint: severity rating on a 8-point ordinal scale at day 15.
T160 18340-18455 Sentence denotes • Comparison of remdesivir vs. hydroxychloroquine vs. remdesivir plus hydroxychloroquine in patients with COVID-19.
T161 18456-18514 Sentence denotes Open-label adaptive RCT (NCT04321616, not yet recruiting).
T162 18515-18585 Sentence denotes Primary endpoint: all-cause in-hospital mortality (follow-up 3 weeks).
T163 18586-18755 Sentence denotes • Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. lopinavir/ritonavir plus interferon beta 1a vs. remdesivir vs. standard of care in patients with COVID-19.
T164 18756-18809 Sentence denotes Double-blind, adaptive RCT (NCT04315948, recruiting).
T165 18810-18881 Sentence denotes Primary endpoint: severity rating on a 7-point ordinal scale at day 15.
T166 18882-18949 Sentence denotes Darunavir/cobicistat Darunavir is an HIV type 1 protease inhibitor.
T167 18950-19130 Sentence denotes Cobicistat is a CYP3A4 inhibitor that boosts darunavir concentrations • Not available • Comparison of darunavir/cobicistat vs. standard of care in patients with COVID-19 pneumonia.
T168 19131-19172 Sentence denotes Open-label RCT (NCT04252274, recruiting).
T169 19173-19287 Sentence denotes Primary endpoint: virologic clearance rate of throat swabs, sputum or lower respiratory tract secretions at day 7.
T170 19288-19594 Sentence denotes Favipiravir Anti-influenza RNA-dependent RNA polymerase inhibitor • In a recent RCT published on a preprint server and comparing 120 COVID-19 patients treated with favipiravir vs. 120 COVID-19 patients receiving umifenovir, higher rates of clinical recovery were observed in patients receiving favipiravir.
T171 19595-19770 Sentence denotes The manuscript is publicly available but still to be peer reviewed [30] • Comparison of favipiravir vs. tocilizumab vs. favipiravir plus tocilizumab in patients with COVID-19.
T172 19771-19812 Sentence denotes Open-label RCT (NCT04310228, recruiting).
T173 19813-19866 Sentence denotes Primary endpoint: clinical cure (follow-up 3 months).
T174 19867-20271 Sentence denotes • 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.
T175 20272-20321 Sentence denotes Open-label RCT (NCT04303299, not yet recruiting).
T176 20322-20389 Sentence denotes Primary endpoint: SARS-CoV-2 eradication time (follow-up 24 weeks).
T177 20390-20498 Sentence denotes • Comparison of hydroxychloroquine plus darunavir/cobicistat vs. standard of care in patients with COVID-19.
T178 20499-20540 Sentence denotes Open-label RCT (NCT04304053, recruiting).
T179 20541-20658 Sentence denotes Primary endpoint: incidence of secondary cases among contacts of a case and contacts of contacts (follow-up 14 days).
T180 20659-20758 Sentence denotes • Comparison of chloroquine plus favipiravir vs. favipiravir vs. placebo in patients with COVID-19.
T181 20759-20802 Sentence denotes Double-blind RCT (NCT04319900, recruiting).
T182 20803-20974 Sentence denotes Primary endpoints: (a) time to improvement/recovery and frequency of improvement/recovery (follow-up 10 days); (b) time to negative swab/sputum RT-PCR (follow-up 10 days).
T183 20975-21050 Sentence denotes • Comparison of favipiravir vs. standard of care in patients with COVID-19.
T184 21051-21100 Sentence denotes Open-label RCT (NCT04333589, not yet recruiting).
T185 21101-21213 Sentence denotes Primary endpoint: viral nucleic acid test negative conversion rate in nasopharyngeal swabs (follow-up 5 months).
T186 21214-21618 Sentence denotes • 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.
T187 21619-21668 Sentence denotes Open-label RCT (NCT04303299, not yet recruiting).
T188 21669-21736 Sentence denotes Primary endpoint: SARS-CoV-2 eradication time (follow-up 24 weeks).
T189 21737-22029 Sentence denotes Umifenovir Anti-influenza membrane fusion inhibitor • In a recent RCT published on a preprint server and comparing 120 COVID-19 patients treated with favipiravir vs. 120 COVID-19 patients receiving umifenovir, higher rates of clinical recovery were observed in patients receiving favipiravir.
T190 22030-22186 Sentence denotes The manuscript is publicly available but still to be peer reviewed [30] • Comparison of umifenovir vs. standard of care in patients with COVID-19 pneumonia.
T191 22187-22236 Sentence denotes Open-label RCT (NCT04260594, not yet recruiting).
T192 22237-22305 Sentence denotes Primary endpoint: virus negative conversion rate (follow-up 7 days).
T193 22306-22685 Sentence denotes Chloroquine, hydroxychloroquine Some proposed mechanisms are the following: increase in the endosomal Ph necessary for the virus/host cell fusion; interference with the glycosylation of cell receptors; immunomodulatory activity • Not available • Comparison of different hydroxychloroquine dosages vs. placebo in three cohorts (outpatients, inpatients, healthcare workers a risk).
T194 22686-22810 Sentence denotes Double-blind RCT for outpatients and healthcare workers and open-label RCT for inpatients (NCT04329923, not yet recruiting).
T195 22811-23008 Sentence denotes Primary endpoints: (a) release from quarantine (outpatients, follow-up 14 days); (b) discharge (inpatients, follow-up 14 days); (c) development of COVID-19 (healthcare workers, follow-up 2 months).
T196 23009-23095 Sentence denotes • Comparison of hydroxychloroquine vs. ascorbic acid in contacts of COVID-19 patients.
T197 23096-23147 Sentence denotes Double-blind RCT (NCT04328961, not yet recruiting).
T198 23148-23216 Sentence denotes Primary endpoint: laboratory-confirmed COVID-19 (follow-up 14 days).
T199 23217-23353 Sentence denotes • Comparison of tocilizumab plus hydroxychloroquine plus azithromycin vs. tocilizumab plus hydroxychloroquine in patients with COVID-19.
T200 23354-23403 Sentence denotes Open-label RCT (NCT04332094, not yet recruiting).
T201 23404-23631 Sentence denotes Primary endpoints: (a) in-hospital mortality (follow-up 2 weeks); (b) need for mechanical ventilation in the ICU (follow-up 2 weeks).• Comparison of ciclesonide plus hydroxychloroquine vs. ciclesonide in patients with COVID-19.
T202 23632-23681 Sentence denotes Open-label RCT (NCT04330586, not yet recruiting).
T203 23682-23755 Sentence denotes Primary endpoint: SARS-CoV-2 eradication (based on virus load) at day 14.
T204 23756-23882 Sentence denotes • Comparison of hydroxychloroquine vs. placebo in patients with COVID-19 and under biological treatment and/or JAK inhibitors.
T205 23883-23934 Sentence denotes Double-blind RCT (NCT04330495, not yet recruiting).
T206 23935-24145 Sentence denotes Primary endpoints: (a) incidence rate of COVID-19 (follow-up 27 weeks); (b) prevalence of COVID-19 (follow-up 27 weeks); (c) case fatality rate (follow-up 27 weeks); (d) ICU admission rate (follow-up 27 weeks).
T207 24146-24254 Sentence denotes • Comparison of hydroxychloroquine vs. placebo for the prevention of COVID-19 in healthcare workers at risk.
T208 24255-24306 Sentence denotes Double-blind RCT (NCT04328467, not yet recruiting).
T209 24307-24369 Sentence denotes Primary endpoint: prevalence of COVID-19 (follow-up 12 weeks).
T210 24370-24482 Sentence denotes • Comparison of chemoprophylaxis with lopinavir/ritonavir vs. placebo in healthcare workers exposed to COVID-19.
T211 24483-24534 Sentence denotes Double-blind RCT (NCT04328285, not yet recruiting).
T212 24535-24552 Sentence denotes Primary endpoint:
T213 24553-24641 Sentence denotes Occurrence of a symptomatic or asymptomatic SARS-CoV-2 infection (follow-up 2.5 months).
T214 24642-24763 Sentence denotes • Comparison of hydroxychloroquine vs. placebo in symptomatic COVID-19 patients or exposed healthcare workers/households.
T215 24764-24807 Sentence denotes Double-blind RCT (NCT04308668, recruiting).
T216 24808-24955 Sentence denotes Primary endpoints: (a) incidence of symptomatic COVID-19 among asymptomatic participants; (b) severity rating on a 3-point ordinal scale at day 14.
T217 24956-25071 Sentence denotes • Comparison of remdesivir vs. hydroxychloroquine vs. remdesivir plus hydroxychloroquine in patients with COVID-19.
T218 25072-25130 Sentence denotes Open-label adaptive RCT (NCT04321616, not yet recruiting).
T219 25131-25201 Sentence denotes Primary endpoint: all-cause in-hospital mortality (follow-up 3 weeks).
T220 25202-25313 Sentence denotes • Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. losartan vs. placebos in patients with COVID-19.
T221 25314-25375 Sentence denotes Double-blind, adaptive RCT (NCT04328012, not yet recruiting).
T222 25376-25452 Sentence denotes Primary endpoint: NIAID COVID-19 Ordinal Severity Scale (follow-up 60 days).
T223 25453-25611 Sentence denotes • Comparison of convalescent plasma plus hydroxychloroquine plus azithromycin vs. hydroxychloroquine plus azithromycin in hospitalized patients with COVID-19.
T224 25612-25661 Sentence denotes Open-label RCT (NCT04332835, not yet recruiting).
T225 25662-25841 Sentence denotes Primary endpoints: (a) change in virus load at days 0, 4, 7, 14 and 28; (b) change in IgM COVID-19 titers at days 0, 4, 7, 14 and 28; (c) change in IgG at days 0, 4, 7, 14 and 28.
T226 25842-26011 Sentence denotes • Comparison of lopinavir/ritonavir vs. hydroxychloroquine vs. lopinavir/ritonavir plus interferon beta-1a vs. remdesivir vs. standard of care in patients with COVID-19.
T227 26012-26065 Sentence denotes Double-blind, adaptive RCT (NCT04315948, recruiting).
T228 26066-26137 Sentence denotes Primary endpoint: severity rating on a 7-point ordinal scale at day 15.
T229 26138-26500 Sentence denotes Methylprednisolone A subgroup of patients with severe COVID-19 might develop a cytokine storm syndrome which causes rapidly progressive pneumonia, ARDS and clinical deterioration and corticosteroids administration may halt the dysregulated cytokine release • Not available • Comparison of methylprednisolone vs. standard of care in patients with severe COVID-19.
T230 26501-26542 Sentence denotes Open-label RCT (NCT04244591, recruiting).
T231 26543-26609 Sentence denotes Primary endpoint: lower Murray lung injury score at days 7 and 14.
T232 26610-26692 Sentence denotes • Comparison of methylprednisolone vs. standard of care in patients with COVID-19.
T233 26693-26734 Sentence denotes Open-label RCT (NCT04273321, recruiting).
T234 26735-26791 Sentence denotes Primary endpoint: treatment failure (follow-up 14 days).
T235 26792-26992 Sentence denotes • Comparison of inhaled alpha interferon plus methylprednisolone plus umifenovir vs. thalidomide plus inhaled alpha interferon plus methylprednisolone plus umifenovir in patients with severe COVID-19.
T236 26993-27044 Sentence denotes Double-blind RCT (NCT04273581, not yet recruiting).
T237 27045-27112 Sentence denotes Primary endpoint: time to clinical improvement (follow-up 28 days).
T238 27113-27195 Sentence denotes • Comparison of different dosages of methylprednisolone in patients with COVID-19.
T239 27196-27237 Sentence denotes Open-label RCT (NCT04263402, recruiting).
T240 27238-27319 Sentence denotes Primary endpoints: (a) disease readmission at day 7; (b) critical stage at day 7.
T241 27320-27428 Sentence denotes • Comparison of siltuximab (anti–IL-6 monoclonal antibody) vs. methylprednisolone in patients with COVID-19.
T242 27429-27478 Sentence denotes Open-label RCT (NCT04329650, not yet recruiting).
T243 27479-27530 Sentence denotes Primary endpoint: ICU admission (follow-up 29 days)
T244 27531-27647 Sentence denotes Tocilizumab Humanized monoclonal IgG1 antibody, tocilizumab inhibits both membrane-bound and soluble IL-6 receptors.
T245 27648-27898 Sentence denotes IL-6, is one of the main drivers of immunologic response and symptoms in patients with dysregulated cytokine release that has been observed in severe COVID-19 • Not available • Comparison of tocilizumab vs. standard of care in patients with COVID-19.
T246 27899-27948 Sentence denotes Open-label RCT (NCT04331808, not yet recruiting).
T247 27949-28051 Sentence denotes Primary endpoint: WHO progression scale at day 7 and 14 (severity rating on a 10-point ordinal scale).
T248 28052-28155 Sentence denotes • Comparison of favipiravir vs. tocilizumab vs. favipiravir plus tocilizumab in patients with COVID-19.
T249 28156-28197 Sentence denotes Open-label RCT (NCT04310228, recruiting).
T250 28198-28251 Sentence denotes Primary endpoint: clinical cure (follow-up 3 months).
T251 28252-28331 Sentence denotes • Comparison of tocilizumab vs. placebo in hospitalized patients with COVID-19.
T252 28332-28383 Sentence denotes Double-blind RCT (NCT04320615, not yet recruiting).
T253 28384-28455 Sentence denotes Primary endpoint: severity rating on a 7-point ordinal scale at day 28.
T254 28456-28592 Sentence denotes • Comparison of tocilizumab plus hydroxychloroquine plus azithromycin vs. tocilizumab plus hydroxychloroquine in patients with COVID-19.
T255 28593-28642 Sentence denotes Open-label RCT (NCT04332094, not yet recruiting).
T256 28643-28776 Sentence denotes Primary endpoints: (a) in-hospital mortality (follow-up 2 weeks); (b) need for mechanical ventilation in the ICU (follow-up 2 weeks).
T257 28777-28932 Sentence denotes • Comparison of chloroquine analog (GNS651) vs. tocilizumab vs. nivolumab vs. standard of care in patients with advanced or metastatic cancer and COVID-19.
T258 28933-28982 Sentence denotes Open-label RCT (NCT04333914, not yet recruiting).
T259 28983-29000 Sentence denotes Primary endpoint:
T260 29001-29017 Sentence denotes 28-day survival.
T261 29018-29219 Sentence denotes • Comparison of tocilizumab intravenously vs. tocilizumab subcutaneously vs. sarilumab (anti-interleukin 6 receptor α monoclonal antibody) subcutaneously vs. standard of care in patients with COVID-19.
T262 29220-29269 Sentence denotes Open-label RCT (NCT04322773, not yet recruiting).
T263 29270-29363 Sentence denotes Primary endpoint: time to independence from supplementary oxygen therapy (follow-up 28 days).
T264 29364-29565 Sentence denotes • Comparison of tocilizumab vs. anakinra (recombinant IL-1 receptor antagonist) vs. siltuximab vs. anakinra plus siltuximab vs. anakinra plus tocilizumab vs. standard of care in patients with COVID-19.
T265 29566-29615 Sentence denotes Open-label RCT (NCT04330638, not yet recruiting).
T266 29616-29683 Sentence denotes Primary endpoint: time to clinical improvement (follow-up 15 days).
T267 29684-29800 Sentence denotes • Comparison of carrimycin vs. lopinavir/ritonavir or umifenovir or chloroquine in patients with COVID-19 pneumonia.
T268 29801-29850 Sentence denotes Open-label RCT (NCT04286503, not yet recruiting).
T269 29851-30033 Sentence denotes 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.
T270 30034-30071 Sentence denotes Anakinra Antagonist of IL-1 receptor.
T271 30072-30328 Sentence denotes IL-1 is one of the main drivers of immunologic response and symptoms in patients with cytokine-release syndrome. • Not available • Comparison of anakinra vs. emapalumab (anti–interferon γ monoclonal antibody) vs. standard of care in patients with COVID-19.
T272 30329-30378 Sentence denotes Open-label RCT (NCT04324021, not yet recruiting).
T273 30379-30425 Sentence denotes Primary endpoint: treatment success at day 15.
T274 30426-30627 Sentence denotes • Comparison of tocilizumab vs. anakinra (recombinant IL-1 receptor antagonist) vs. siltuximab vs. anakinra plus siltuximab vs. anakinra plus tocilizumab vs. standard of care in patients with COVID-19.
T275 30628-30677 Sentence denotes Open-label RCT (NCT04330638, not yet recruiting).
T276 30678-30745 Sentence denotes Primary endpoint: time to clinical improvement (follow-up 15 days).
T277 30746-30879 Sentence denotes Off-label drugs mostly provided in Italy during the first phase of the COVID-19 pandemic according to the authors' direct experience.
T278 30880-31063 Sentence denotes Of note, there are also registered RCT for other drugs to be investigated in patients with COVID-19 (e.g. the Janus kinase family inhibitors ruxolitinib, baricitinib and tofacitinib).
T279 31064-31583 Sentence denotes ARDS = acute respiratory distress syndrome; CI, confidence interval; COVID-19, coronavirus disease 2019; CT, computed tomography; EOT, end of treatment; HR, hazard ratio; Ig, immunoglobulin; IL-1, interleukin 1; IQR, interquartile range; ITT, intent to treat; mITT, modified intent to treat; Pao2/Fio2, of arterial oxygen partial pressure to fractional inspired oxygen; RCT, randomized controlled trial; RT-PCR, real-time PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WHO, World Health Organization.