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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
      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
            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
            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
                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
                  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
                    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 (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
                      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 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
                        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
                          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 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
                            Singh, 2020 OBShydroxychloroquinecontrolCOVID 19 hospitalizedcritical
                            -/- inconclusive

                              COVID 19 all comers meta-analysis

                              ChiCTR2000030054-HCQ (Chen), 2020
                               
                              ChiCTR2000030054
                              RCThydroxychloroquinestandard of careCOVID 19 all comershigh
                              18/12 inconclusive
                                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

                                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
                                HC-nCoV (Shanghai), 2020
                                 
                                NCT04261517
                                RCThydroxychloroquinestandard of careCOVID-19 mild to moderatesome concern
                                15/15 inconclusive
                                  NCT04333654, 2020
                                   
                                  NCT04333654
                                  RCThydroxychloroquinestandard of careCOVID-19 mild to moderateNA
                                  -/- inconclusive
                                    NCT04342650, 2020
                                     
                                    NCT04342650
                                    RCTchloroquineplaceboCOVID-19 mild to moderateNA
                                    -/- inconclusive
                                      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
                                        Min, 2020 OBShydroxychloroquinecontrolCOVID-19 mild to moderateNA
                                        20/20 inconclusive

                                          COVID-19 severe or critically meta-analysis

                                          HYDRA, 2020
                                           
                                          NCT04315896
                                          RCThydroxychloroquineplaceboCOVID-19 severe or criticallyNA
                                          75/77 inconclusive
                                          • inconclusive 1 % decrease in deaths (PE)
                                          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
                                          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

                                            COVID 19 outpatients meta-analysis

                                            BCN PEP-CoV-2-Research group (Mitja et al. Clin Infect Dis), 2020
                                             
                                            NCT04304053
                                            RCThydroxychloroquinestandard of careCOVID 19 outpatientssome concern
                                            137/157 safety concern
                                            • statistically significant 25.5-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
                                            • statistically significant 177.2-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
                                            BCN PEP-CoV-2-Study 2 (Mitja Lancet), 2020
                                             
                                            NCT04304053
                                            RCThydroxychloroquinestandard of careCOVID 19 outpatientssome concern
                                            142/165 inconclusive
                                              COMIHY, 2020
                                               
                                              NCT04340544
                                              RCThydroxychloroquinestandard of careCOVID 19 outpatientsNA
                                              -/- inconclusive
                                                COVID-PEP Severity (Skipper), 2020
                                                 
                                                NCT04308668
                                                RCThydroxychloroquinecontrolCOVID 19 outpatientssome concern
                                                244/247 no results
                                                  change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117)
                                                  COVID-PEP Severity (Skipper), 2020
                                                   
                                                  NCT04308668
                                                  RCThydroxychloroquineplaceboCOVID 19 outpatientssome concern
                                                  244/247 safety concern
                                                  • statistically significant 1.8-fold increase in adverse events with a moderate degree of certainty due to some concern in risk of bias
                                                  change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, −0.27 points [95% CI, −0.61 to 0.07 points]; P = 0.117)
                                                  PATCH-cohort 1, 2020
                                                   
                                                  NCT04329923
                                                  RCThydroxychloroquinecontrolCOVID 19 outpatientsNA
                                                  -/- inconclusive
                                                    Q-PROTECT -HCQ alone, 2020
                                                     
                                                    NCT04349592
                                                    RCThydroxychloroquineplaceboCOVID 19 outpatientsNA
                                                    152/152 inconclusive
                                                    • inconclusive 5 % increase in PCR-negative conversion,PCR-negative conversion (7-day) (PE)

                                                    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).