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Study Ref. studied treatmentcontrol treatmentpatientsstudy risk of biassample sizes Results

COVID 19 hospitalized meta-analysis

Abd-Elsalam, 2020
 
NCT04353336
RCThydroxychloroquinestandard of careCOVID 19 hospitalizedsome concern
97/97 inconclusive
    ARCHAIC -hydroxychloroquine, 2020
     
    NL8490
    RCThydroxychloroquinestandard of careCOVID 19 hospitalizedNA
    9/6 inconclusive
      BRACE CORONA, 2020 RCTdiscontinuation of ACEI/ARBcontrolCOVID 19 hospitalizedsome concern
      334/325 inconclusive
        CCAP-1, 2020
         
        NCT04345289
        RCThydroxychloroquinestandard of careCOVID 19 hospitalizedNA
        -/- inconclusive
          Chen, 2020
           
          NCT04384380
          RCThydroxychloroquinestandard of careCOVID 19 hospitalizedsome concern
          21/12 inconclusive
            Duke university HCQ, 2020
             
            NCT04335552
            RCThydroxychloroquinestandard of careCOVID 19 hospitalizedNA
            4/2 no results
              discontinued, found in Axfors et al. meta-analysis
              Duke university HCQ-AZI, 2020
               
              NCT04335552
              RCThydroxychloroquine plus macrolidesstandard of careCOVID 19 hospitalizedNA
              -/- inconclusive
                Elgazzar - treatment, 2020 RCTivermectinhydroxychloroquineCOVID 19 hospitalizedhigh
                200/200 suggested
                • suggested 93 % decrease in deaths but with a low degree of certainty due to high risk of bias
                HAHPS, 2020
                 
                NCT04329832
                RCThydroxychloroquineazithromycinCOVID 19 hospitalizedsome concern
                42/43 inconclusive
                • inconclusive 7 % increase in clinical deterioration (PE) with a moderate degree of certainty due to some concern in risk of bias
                Hashim A, 2020
                 
                NCT04591600
                RCTivermectinstandard of careCOVID 19 hospitalizedsome concern
                70/70 inconclusive
                • inconclusive 52 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                Hashim A, 2020
                 
                NCT04591600
                RCTdoxycyclinestandard of careCOVID 19 hospitalizedsome concern
                70/70 inconclusive
                • inconclusive 52 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                Huang, 2020
                 
                ChiCTR2000029542
                RCTchloroquinelopinavir/ritonavirCOVID 19 hospitalizedsome concern
                10/12 inconclusive
                  HYCOVID, 2020
                   
                  NCT04325893
                  RCThydroxychloroquineplaceboCOVID 19 hospitalizedsome concern
                  124/123 inconclusive
                  • inconclusive 12 % increase in death or ventilation (PE) with a moderate degree of certainty due to some concern in risk of bias
                  NO COVID-19 (Lyngbakken), 2020
                   
                  NCT04316377
                  RCThydroxychloroquinestandard of careCOVID 19 hospitalizedsome concern
                  27/26 inconclusive
                    Nojomi, 2020
                     
                    IRCT20180725040596N2
                    RCTumifenovir (arbidol)lopinavir/ritonavirCOVID 19 hospitalizedsome concern
                    50/50 inconclusive
                      Nojomi, 2020
                       
                      IRCT20180725040596N2
                      RCTlopinavir/ritonavirumifenovir (arbidol)COVID 19 hospitalizedsome concern
                      50/50 inconclusive
                        OAHU-COVID19, 2020
                         
                        NCT04345692
                        RCThydroxychloroquinestandard of careCOVID 19 hospitalizedNA
                        10/6 inconclusive
                          ORCHID, 2020
                           
                          NCT04332991
                          RCThydroxychloroquineplaceboCOVID 19 hospitalizedlow
                          242/237 inconclusive
                          • inconclusive 2 % increase in clinical improvement (PE) with a high degree of certainty due to low risk of bias
                          PROTECT B, 2020
                           
                          NCT04338698
                          RCToseltamiviroseltamivirCOVID 19 hospitalizedNA
                          -/- inconclusive
                            PROTECT B, 2020
                             
                            NCT04338698
                            RCThydroxychloroquineoseltamivirCOVID 19 hospitalizedNA
                            -/- inconclusive
                              RECOVERY, 2020
                               
                              NCT04381936
                              RCThydroxychloroquinestandard of careCOVID 19 hospitalizedsome concern
                              1561/3155 safety concern
                              • inconclusive 9 % increase in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                              • statistically significant 14 % increase in death or ventilation with a moderate degree of certainty due to some concern in risk of bias
                              RECOVERY, 2020
                               
                              NCT04381936
                              RCTlopinavir/ritonavirstandard of careCOVID 19 hospitalizedsome concern
                              1616/3424 inconclusive
                              • inconclusive 3 % increase in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                              the trial Steering Committee concluded that there is no beneficial effect of lopinavir-ritonavir in patients hospitalised with COVID-19 and closed randomisation to that treatment arm
                              RECOVERY-AZI (Horby), 2020
                               
                              NCT04381936
                              RCTazithromycinstandard of careCOVID 19 hospitalizedsome concern
                              2582/5182 inconclusive
                              • inconclusive 0 % increase in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                              Preliminary findings based on a data cut on 30 November. Final results will be made available after the last patient has completed the 28-day follow-up period for the primary outcome on 25 December 2020
                              REPLACE, 2020
                               
                              NCT04338009
                              RCTRenin-angiotensin-system-acting agentscontrolCOVID 19 hospitalizedNA
                              77/75 inconclusive
                                Sekhavati, 2020 RCTlopinavir/ritonavirlopinavir/ritonavirCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Sekhavati, 2020 RCTlopinavir/ritonavirhydroxychloroquineCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Sekhavati, 2020 RCTazithromycinlopinavir/ritonavirCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Sekhavati, 2020 RCTazithromycinhydroxychloroquineCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Sekhavati, 2020 RCThydroxychloroquinelopinavir/ritonavirCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Sekhavati, 2020 RCThydroxychloroquinehydroxychloroquineCOVID 19 hospitalizedsome concern
                                56/55 inconclusive
                                • inconclusive 51 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                SOLIDARITY (lopi/rito), 2020
                                 
                                NCT04315948
                                RCTlopinavir/ritonavirstandard of careCOVID 19 hospitalizedsome concern
                                1399/1372 inconclusive
                                • inconclusive 0 % increase in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
                                SOLIDARITY (remdesivir), 2020
                                 
                                NCT04315948
                                RCTremdesivircontrolCOVID 19 hospitalizedsome concern
                                2750/4088 inconclusive
                                • inconclusive 5 % decrease in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                SOLIDARITY (WHO study) HCQ, 2020
                                 
                                NCT04315948
                                RCThydroxychloroquinestandard of careCOVID 19 hospitalizedsome concern
                                947/906 inconclusive
                                • inconclusive 19 % increase in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                Tang, 2020
                                 
                                ChiCTR2000029868
                                RCTchloroquine and derivativesstandard of careCOVID 19 hospitalizedhigh
                                75/75 inconclusive
                                  Tang, 2020
                                   
                                  ChiCTR2000029868
                                  RCThydroxychloroquinestandard of careCOVID 19 hospitalizedhigh
                                  75/75 safety concern
                                  • statistically significant 3.5-fold increase in adverse events but with a low degree of certainty due to high risk of bias
                                  TEACH, 2020
                                   
                                  NCT04369742
                                  RCThydroxychloroquineplaceboCOVID 19 hospitalizedsome concern
                                  67/61 inconclusive
                                  • inconclusive 80 % increase in clinical deterioration (PE) with a moderate degree of certainty due to some concern in risk of bias
                                  • inconclusive 16 % increase in adverse events (PE) with a moderate degree of certainty due to some concern in risk of bias
                                  Rodriguez-Molinero, 2020 OBSazithromycinCOVID 19 hospitalizedNA
                                  -/- ongoing
                                    Our study did not find a benefit associated with the use of azithromycin in terms of respiratory function (SAFI)
                                    Rodriguez-Molinero, 2020 OBSazithromycincontrolCOVID 19 hospitalizedNA
                                    -/- inconclusive
                                      Our study did not find a benefit associated with the use of azithromycin in terms of respiratory function (SAFI)
                                      Arshad (HCQ AZ), 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedcritical
                                      783/409 suggested
                                      • suggested 71 % decrease in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                                      Arshad (HCQ), 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                                      1202/409 suggested
                                      • suggested 66 % decrease in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                                      Belgian Collaborative Group on COVID-19, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedserious
                                      4542/3533 suggested
                                      • suggested 32 % decrease in deaths,deaths (time to event analysis only) but with a low degree of certainty due to high risk of bias
                                      Chen, 2020 OBSlopinavir/ritonavircontrolCOVID 19 hospitalizedcritical
                                      163/121 inconclusive
                                        Chen, 2020 OBSumifenovir (arbidol)controlCOVID 19 hospitalizedcritical
                                        163/121 inconclusive
                                          Chen, 2020 OBSoseltamivircontrolCOVID 19 hospitalizedcritical
                                          163/121 inconclusive
                                            Chen, 2020 OBSchloroquinecontrolCOVID 19 hospitalizedcritical
                                            163/121 inconclusive
                                              Chen, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                                              163/121 safety concern
                                              • statistically significant 51 % decrease in clinical improvement,clinical improvement (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                                              Davido, 2020
                                               
                                              NCT04453501
                                              OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedcritical
                                              52/40 suggested
                                              • suggested 55 % decrease in death or transfer to ICU but with a very low degree of certainty due to critical risk of bias
                                              Geleris, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedserious
                                              811/565 inconclusive
                                                Huang, 2020 OBSchloroquinecontrolCOVID 19 hospitalizedcritical
                                                197/176 suggested
                                                • suggested 5.1-fold increase in PCR-negative conversion (14-day) but with a very low degree of certainty due to critical risk of bias
                                                ICON, 2020 OBSivermectinstandard of careCOVID 19 hospitalizedNA
                                                173/107 suggested
                                                • suggested 53 % decrease in deaths (PE)
                                                Lagier, 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedcritical
                                                3119/618 suggested
                                                • suggested 51 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
                                                • suggested 70 % decrease in clinical deterioration but with a very low degree of certainty due to critical risk of bias
                                                • suggested 62 % decrease in hospitalization but with a very low degree of certainty due to critical risk of bias
                                                Magagnoli (HC), 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedserious
                                                97/158 safety concern
                                                • safety concern with statistically significant 1.6-fold increase in deaths,deaths (time to event analysis only)
                                                Novales, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                                                123/43 suggested
                                                • suggested 93 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
                                                Paccoud, 2020 OBShydroxychloroquinestandard of careCOVID 19 hospitalizedserious
                                                38/46 inconclusive
                                                  Rosenberg, 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedserious
                                                  -/- safety concern
                                                  • safety concern with statistically significant 1.1-fold increase in cardiac arrest
                                                  • statistically significant 1.2-fold increase in arrhythmia but with a low degree of certainty due to high risk of bias
                                                  Rosenberg, 2020 OBSazithromycincontrolCOVID 19 hospitalizedserious
                                                  -/- inconclusive
                                                    Rosenberg, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedserious
                                                    -/- safety concern
                                                    • safety concern with 91 % increase in cardiac arrest (not statistically significant)
                                                    Sbidian (HCQ alone), 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                                                    623/3792 safety concern
                                                    • statistically significant 25 % increase in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                                                    Sbidian (HCQ plus AZI), 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedcritical
                                                    227/3792 inconclusive
                                                      Singh, 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 hospitalizedcritical
                                                      -/- inconclusive
                                                        Singh, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                                                        -/- inconclusive

                                                          COVID 19 all comers meta-analysis

                                                          Chang Chen et al., 2020
                                                           
                                                          ChiCTR2000030254
                                                          RCTfavipiravir umifenovir (arbidol)COVID 19 all comerssome concern
                                                          120/120 inconclusive
                                                            ChiCTR2000030054-HCQ (Chen), 2020
                                                             
                                                            ChiCTR2000030054
                                                            RCThydroxychloroquinestandard of careCOVID 19 all comershigh
                                                            18/12 inconclusive
                                                              ELACOI (Standard of care), 2020
                                                               
                                                              NCT04252885
                                                              RCTumifenovir (arbidol)standard of careCOVID 19 all comerssome concern
                                                              16/7 inconclusive
                                                                jRCTs041190120, 2020
                                                                 
                                                                jRCTs041190120
                                                                RCTfavipiravir favipiravir COVID 19 all comershigh
                                                                44/45 inconclusive
                                                                • inconclusive 42 % increase in PCR-negative conversion,PCR-negative conversion (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
                                                                Lou Y, 2020
                                                                 
                                                                ChiCTR2000029544
                                                                RCTbaloxavir marboxilstandard of careCOVID 19 all comerssome concern
                                                                10/10 inconclusive
                                                                • inconclusive 88 % decrease in PCR-negative conversion (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                Lou Y - FAVIPIRAVIR, 2020
                                                                 
                                                                ChiCTR2000029544
                                                                RCTfavipiravir standard of careCOVID 19 all comerssome concern
                                                                10/10 inconclusive
                                                                • inconclusive 82 % decrease in PCR-negative conversion,PCR-negative conversion (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                NCT04310228-FAVI (Zhao), 2020
                                                                 
                                                                ChiCTR2000030894
                                                                RCTfavipiravir tocilizumab COVID 19 all comerssome concern
                                                                -/- inconclusive
                                                                • inconclusive 68 % decrease in clinical improvement,clinical improvement (14-day),clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                NIH NIAID ACTT-1, 2020
                                                                 
                                                                NCT04280705
                                                                RCTremdesivirplaceboCOVID 19 all comerssome concern
                                                                538/521 suggested
                                                                • suggested 32 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                Calik, 2020 OBSfavipiravir hydroxychloroquineCOVID 19 all comerscritical
                                                                -/- no results
                                                                  Li, 2020 OBSRenin-angiotensin-system-acting agentscontrolCOVID 19 all comerscritical
                                                                  -/- inconclusive
                                                                    Magagnoli (HC AZ), 2020 OBShydroxychloroquine plus macrolidescontrolCOVID 19 all comersserious
                                                                    113/158 inconclusive
                                                                      Meng, 2020 OBSRenin-angiotensin-system-acting agentscontrolCOVID 19 all comerscritical
                                                                      17/25 inconclusive
                                                                        Yang, 2020 OBSRenin-angiotensin-system-acting agentscontrolCOVID 19 all comersserious
                                                                        43/83 inconclusive
                                                                          Zhang, 2020 OBSRenin-angiotensin-system-acting agentscontrolCOVID 19 all comersserious
                                                                          188/940 suggested
                                                                          • suggested 63 % decrease in deaths but with a low degree of certainty due to high risk of bias
                                                                          Bean, 2020 OBSRenin-angiotensin-system-acting agentscontrolCOVID 19 all comersserious
                                                                          37/168 suggested
                                                                          • suggested 71 % decrease in death or transfer to ICU but with a low degree of certainty due to high risk of bias
                                                                          Yan et al., 2020 OBSangiotensin converting enzyme inhibitors (ACEIs)controlCOVID 19 all comerscritical
                                                                          -/- inconclusive
                                                                            Yan et al., 2020 OBSangiotensin receptor blockers (ARBs)controlCOVID 19 all comerscritical
                                                                            -/- inconclusive
                                                                              Cai -FAVIPIRAVIR, 2020
                                                                               
                                                                              ChiCTR2000029600
                                                                              NRafavipiravir lopinavir/ritonavirCOVID 19 all comersNA
                                                                              35/45 suggested
                                                                              • suggested 5.5-fold increase in clinical improvement,clinical improvement (14-day)
                                                                              Cai -FAVIPIRAVIR, 2020
                                                                               
                                                                              ChiCTR2000029600
                                                                              NRafavipiravir interferonCOVID 19 all comersNA
                                                                              35/45 suggested
                                                                              • suggested 5.5-fold increase in clinical improvement,clinical improvement (14-day)
                                                                              Gautret et al., 2020 NRahydroxychloroquinecontrolCOVID 19 all comersserious
                                                                              20/16 suggested
                                                                              • suggested 15.3-fold increase in PCR-negative conversion (PE) but with a low degree of certainty due to high risk of bias
                                                                              a viral load reduction/disappearance is claimed but the numerous methological limits preclude any strong conclusion

                                                                              COVID-19 mild to moderate meta-analysis

                                                                              Ahmed, 2020 RCTivermectinplaceboCOVID-19 mild to moderatehigh
                                                                              48/24 suggested
                                                                              • suggested 3.1-fold increase in PCR-negative conversion (time to event analysis only),PCR-negative conversion (14-day) (PE) but with a low degree of certainty due to high risk of bias
                                                                              Paradoxically comparison of day 7 and 14 virological clearance between ivermectin doxycycline group vs placebo was not statistically significant (HR 2.3[0.6-9.0] and 1.7[0.8-4.0])
                                                                              AVIFAVIR, 2020
                                                                               
                                                                              NCT04434248
                                                                              RCTfavipiravir standard of careCOVID 19 hospitalized, COVID-19 mild to moderatesome concern
                                                                              20/20 suggested
                                                                              • suggested 2.9-fold increase in PCR-negative conversion,PCR-negative conversion (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                              Adverse drug reactions to AVIFAVIR were reported in 7/40 (17.5%) patients, including diarrhea, nausea, vomiting, chest pain and an increase in liver transaminase levels. The adverse drug reactions were mild to moderate and caused early discontinuation of the study drug in 2/40 (5.0%) patients.
                                                                              Chaccour, 2020
                                                                               
                                                                              NCT04390022
                                                                              RCTivermectinplaceboCOVID 19 outpatients, COVID-19 mild to moderatelow
                                                                              12/12 inconclusive
                                                                              • inconclusive 8 % decrease in PCR-negative conversion,PCR-negative conversion (7-day) (PE) with a high degree of certainty due to low risk of bias
                                                                              Chachar, 2020 RCTivermectinstandard of careCOVID-19 mild to moderatesome concern
                                                                              25/25 inconclusive
                                                                              • inconclusive 19 % increase in clinical improvement,clinical improvement (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                              Coalition Covid-19 Brazil I (Cavalcanti) - HCQ AZI, 2020
                                                                               
                                                                              NCT04322123
                                                                              RCThydroxychloroquine plus macrolidesstandard of careCOVID-19 mild to moderatesome concern
                                                                              217/227 safety concern
                                                                              • inconclusive 1 % decrease in clinical deterioration (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                              • statistically significant 8.8-fold increase in long QT with a moderate degree of certainty due to some concern in risk of bias
                                                                              Coalition Covid-19 Brazil I (Cavalcanti)-Hydroxychloroquine, 2020
                                                                               
                                                                              NCT04322123
                                                                              RCThydroxychloroquinestandard of careCOVID-19 mild to moderatesome concern
                                                                              221/227 safety concern
                                                                              • statistically significant 74 % increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
                                                                              Dabbous HM, 2020
                                                                               
                                                                              NCT04349241
                                                                              RCTfavipiravir standard of careCOVID-19 mild to moderatesome concern
                                                                              50/50 inconclusive
                                                                                ELACOI (lopinavir/ritonavir), 2020
                                                                                 
                                                                                NCT04252885
                                                                                RCTlopinavir/ritonavirstandard of careCOVID-19 mild to moderatesome concern
                                                                                21/7 inconclusive
                                                                                  ELACOI (Lopinavir/ritonavir), 2020
                                                                                   
                                                                                  NCT04252885
                                                                                  RCTumifenovir (arbidol)lopinavir/ritonavirCOVID-19 mild to moderatesome concern
                                                                                  35/34 inconclusive
                                                                                  • inconclusive 84 % increase in PCR-negative conversion (14-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  • inconclusive 8 % increase in PCR-negative conversion (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  GS-US-540-5774, 10 days, 2020
                                                                                   
                                                                                  NCT04292730
                                                                                  RCTremdesivirstandard of careCOVID-19 mild to moderatesome concern
                                                                                  197/200 suggested
                                                                                  • suggested 58 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  • suggested 88 % increase in clinical improvement (28-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  the primary endpoint was not meet, no odds ratio is reported because theproportional odds assumption was not met
                                                                                  GS-US-540-5774, 5 days, 2020
                                                                                   
                                                                                  NCT04292730
                                                                                  RCTremdesivirstandard of careCOVID-19 mild to moderatesome concern
                                                                                  199/200 conclusif
                                                                                  • demonstrated 65 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  • suggested 53 % increase in clinical improvement (7-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                  HC-nCoV (Shanghai), 2020
                                                                                   
                                                                                  NCT04261517
                                                                                  RCThydroxychloroquinestandard of careCOVID-19 mild to moderatesome concern
                                                                                  15/15 inconclusive
                                                                                    Hung et al., 2020
                                                                                     
                                                                                    NCT04276688
                                                                                    RCTlopinavir/ritonavir, ribavirin and interferon beta-1blopinavir/ritonavirCOVID-19 mild to moderatesome concern
                                                                                    86/41 conclusif
                                                                                    • demonstrated 3.4-fold increase in PCR-negative conversion,PCR-negative conversion (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                    • suggested 2.9-fold increase in clinical improvement,clinical improvement (time to event analysis only) with a moderate degree of certainty due to some concern in risk of bias
                                                                                    Khamis, 2020 RCTfavipiravir standard of careCOVID-19 mild to moderatesome concern
                                                                                    44/45 inconclusive
                                                                                      Krolewiecki, A, 2020
                                                                                       
                                                                                      NCT04381884
                                                                                      RCTivermectinstandard of careCOVID-19 mild to moderatesome concern
                                                                                      30/15 inconclusive
                                                                                        Viral load reduction between baseline and day-5 was also similar between groups
                                                                                        NCT04333654, 2020
                                                                                         
                                                                                        NCT04333654
                                                                                        RCThydroxychloroquinestandard of careCOVID-19 mild to moderateNA
                                                                                        -/- inconclusive
                                                                                          NCT04342650, 2020
                                                                                           
                                                                                          NCT04342650
                                                                                          RCTchloroquineplaceboCOVID-19 mild to moderateNA
                                                                                          -/- inconclusive
                                                                                            NCT04523831 (Mahmud), 2020
                                                                                             
                                                                                            NCT04523831
                                                                                            RCTivermectinstandard of careCOVID-19 mild to moderatehigh
                                                                                            200/200 safety concern
                                                                                            • suggested 89 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
                                                                                            • suggested 93 % increase in clinical improvement (7-day) (PE) but with a low degree of certainty due to high risk of bias
                                                                                            • suggested 56 % decrease in clinical deterioration but with a low degree of certainty due to high risk of bias
                                                                                            • statistically significant 17.6-fold increase in adverse events but with a low degree of certainty due to high risk of bias
                                                                                            results from clinicaltrial.gov
                                                                                            NCT04523831 (Mahmud), 2020
                                                                                             
                                                                                            NCT04523831
                                                                                            RCTdoxycyclinestandard of careCOVID-19 mild to moderatehigh
                                                                                            200/200 safety concern
                                                                                            • suggested 89 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
                                                                                            • suggested 93 % increase in clinical improvement (7-day) (PE) but with a low degree of certainty due to high risk of bias
                                                                                            • suggested 56 % decrease in clinical deterioration but with a low degree of certainty due to high risk of bias
                                                                                            • statistically significant 17.6-fold increase in adverse events but with a low degree of certainty due to high risk of bias
                                                                                            results from clinicaltrial.gov
                                                                                            NCT04542694, 2020
                                                                                             
                                                                                            NCT04542694
                                                                                            RCTfavipiravir standard of careCOVID-19 mild to moderatesome concern
                                                                                            100/100 suggested
                                                                                            • suggested 12.0-fold increase in PCR-negative conversion with a moderate degree of certainty due to some concern in risk of bias
                                                                                            Ren, 2020
                                                                                             
                                                                                            ChiCTR2000029853
                                                                                            RCTazvudineantiviral and associated therapyCOVID-19 mild to moderatesome concern
                                                                                            10/10 suggested
                                                                                            • suggested 27.5-fold increase in PCR-negative conversion (7-day) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            Ruzhentsova T, 2020
                                                                                             
                                                                                            NCT04501783
                                                                                            RCTfavipiravir standard of careCOVID-19 mild to moderatesome concern
                                                                                            112/56 suggested
                                                                                            • suggested 63 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • inconclusive 28 % increase in PCR-negative conversion,PCR-negative conversion (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • suggested 28 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • suggested 50 % increase in clinical improvement (7-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            Udwadia ZF, 2020
                                                                                             
                                                                                            CTRI/2020/05/025114
                                                                                            RCTfavipiravir standard of careCOVID 19 hospitalized, COVID-19 mild to moderatesome concern
                                                                                            75/75 safety concern
                                                                                            • inconclusive 37 % increase in PCR-negative conversion,PCR-negative conversion (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • suggested 75 % increase in clinical improvement,clinical improvement (time to event analysis only),clinical improvement (28-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • suggested 94 % decrease in ventilation (time to event analysis only),ventilation with a moderate degree of certainty due to some concern in risk of bias
                                                                                            • statistically significant 5.4-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
                                                                                            Zhaowei Chen, 2020
                                                                                             
                                                                                            ChiCTR2000029559
                                                                                            RCThydroxychloroquinecontrolCOVID-19 mild to moderatehigh
                                                                                            31/31 inconclusive
                                                                                              Zhaowei Chen, 2020
                                                                                               
                                                                                              ChiCTR2000029559
                                                                                              RCThydroxychloroquinestandard of careCOVID-19 mild to moderatehigh
                                                                                              31/31 suggested
                                                                                              • suggested 2.4-fold increase in clinical improvement but with a low degree of certainty due to high risk of bias
                                                                                              • suggested 2.4-fold increase in radiologic improvement (7-day) but with a low degree of certainty due to high risk of bias
                                                                                              Glorial F, 2020
                                                                                               
                                                                                              NCT04343092
                                                                                              OBSivermectinstandard of careCOVID-19 mild to moderateNA
                                                                                              6/71 inconclusive
                                                                                              • inconclusive 10 % decrease in clinical improvement (PE)
                                                                                              Soto-Becerra, 2020 OBSivermectinstandard of careCOVID 19 hospitalized, COVID-19 mild to moderatemoderate
                                                                                              203/2630 safety concern
                                                                                              • inconclusive 39 % increase in deaths,deaths (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                              • statistically significant 58 % increase in death or transfer to ICU with a moderate degree of certainty due to some concern in risk of bias
                                                                                              Our study reported no beneficial effects of hydroxychloroquine, ivermectin, azithromycin. The HCQ AZIT treatment seems to increase risk for all-cause death
                                                                                              Khan, 2020 OBSivermectinstandard of careCOVID 19 hospitalized, COVID-19 mild to moderateNA
                                                                                              115/133 suggested
                                                                                              • suggested 88 % decrease in deaths
                                                                                              • suggested 7.3-fold increase in clinical improvement
                                                                                              • suggested 88 % decrease in ventilation
                                                                                              Min, 2020 OBShydroxychloroquinecontrolCOVID-19 mild to moderateNA
                                                                                              20/20 inconclusive
                                                                                                Espitia-Hernandez, 2020 NRaazithromycinstandard of careCOVID 19 outpatients, COVID-19 mild to moderateNA
                                                                                                28/7 suggested
                                                                                                • suggested 714.0-fold increase in PCR-negative conversion
                                                                                                Espitia-Hernandez, 2020 NRaivermectinstandard of careCOVID 19 outpatients, COVID-19 mild to moderateNA
                                                                                                28/7 suggested
                                                                                                • suggested 714.0-fold increase in PCR-negative conversion
                                                                                                Spoorthi, 2020 NRaivermectinplaceboCOVID 19 hospitalized, COVID-19 mild to moderateNA
                                                                                                50/50 inconclusive
                                                                                                  Spoorthi, 2020 NRadoxycyclineplaceboCOVID 19 hospitalized, COVID-19 mild to moderateNA
                                                                                                  50/50 inconclusive

                                                                                                    COVID-19 severe or critically meta-analysis

                                                                                                    Cao B, 2020
                                                                                                     
                                                                                                    ChiCTR2000029308
                                                                                                    RCTlopinavir/ritonavirstandard of careCOVID-19 severe or criticallysome concern
                                                                                                    99/100 suggested
                                                                                                    • inconclusive 31 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                                                                                    • suggested 94 % increase in clinical improvement (14-day) with a moderate degree of certainty due to some concern in risk of bias
                                                                                                    CAP-China (Wang et al.), 2020
                                                                                                     
                                                                                                    NCT04257656
                                                                                                    RCTremdesivirplaceboCOVID-19 severe or criticallylow
                                                                                                    158/79 inconclusive
                                                                                                    • inconclusive 23 % increase in clinical improvement,clinical improvement (time to event analysis only) (PE) with a high degree of certainty due to low risk of bias
                                                                                                    COALITION II (Furtado), 2020
                                                                                                     
                                                                                                    NCT04321278
                                                                                                    RCTazithromycinhydroxychloroquineCOVID-19 severe or criticallysome concern
                                                                                                    214/183 inconclusive
                                                                                                      HYDRA, 2020
                                                                                                       
                                                                                                      NCT04315896
                                                                                                      RCThydroxychloroquineplaceboCOVID-19 severe or criticallyNA
                                                                                                      75/77 inconclusive
                                                                                                      • inconclusive 1 % decrease in deaths (PE)
                                                                                                      Niaee (vs placebo), 2020
                                                                                                       
                                                                                                      IRCT20200408046987N1
                                                                                                      RCTivermectincontrolCOVID-19 severe or criticallyhigh
                                                                                                      120/30 suggested
                                                                                                      • suggested 86 % decrease in deaths but with a low degree of certainty due to high risk of bias
                                                                                                      Okumuş, 2020
                                                                                                       
                                                                                                      NCT04646109
                                                                                                      RCTivermectincontrolCOVID-19 severe or criticallyNA
                                                                                                      30/30 inconclusive
                                                                                                        REMAP-CAP-HCQ, 2020
                                                                                                         
                                                                                                        NCT02735707
                                                                                                        RCThydroxychloroquinestandard of careCOVID-19 severe or criticallyNA
                                                                                                        61/81 inconclusive
                                                                                                        • inconclusive 4 % increase in deaths (PE)
                                                                                                        REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia.multi-arm study
                                                                                                        Kocayigit H, 2020 OBSfavipiravir lopinavir/ritonavirCOVID-19 severe or criticallyNA
                                                                                                        65/42 inconclusive
                                                                                                          Camprubi, 2020 OBSivermectinstandard of careCOVID-19 severe or criticallyNA
                                                                                                          13/13 inconclusive
                                                                                                            Mahevas, 2020 OBShydroxychloroquinestandard of careCOVID-19 severe or criticallyserious
                                                                                                            84/97 inconclusive
                                                                                                              Yu, 2020 OBShydroxychloroquinecontrolCOVID-19 severe or criticallycritical
                                                                                                              48/520 suggested
                                                                                                              • suggested 68 % decrease in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias

                                                                                                              PE: primary endpoint; (a): to be demonstrated a result must be statistically significant on a primary endpoint (with multiplicity adjustment if necessary);
                                                                                                              Study risk of bias assessed for the study primary endpoint(s) or the main endpoints in case of no formally defined primary endpoint(s).