Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial

Bosaeed, Mohammad; Mahmoud, Ebrahim; Alharbi, Ahmad; Altayib, Hadeel; Albayat, Hawra; Alharbi, Faisal; Ghalilah, Khalid; Arfaj, Abdulmajid Al; Al-Jishi, Jumana M.; Alarfaj, Abdullatif; AlQahtani, Hajar; AlMutairi, Badriah M.; Almaghaslah, Manar; Alyahya, Nawaf M.; Bawazir, Abdullah; Aleisa, Saud Mohammed Saud; Alsaedy, Abdulrahman; Bouchama, Abderrezak; Alharbi, Malak; Alshamrani, Majid M.; Johani, Sameera Al; Al-Jeraisy, Majed; Alzahrani, Mohammed; Althaqafi, Abdulhakeem; Almarhabi, Hassan; Alotaibi, Athari; Alqahtani, Nasser; Arabi, Yaseen M.; Aldibasi, Omar; Alaskar, Ahmad

doi:10.1007/s40121-021-00496-6

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…The hospital discharge rate was reported in 65 studies including 53,636 patients and 34,247 events. Treatment nodes included in the network were azithromycin, bamlanivimab, baricitinib plus remdesivir, camostat mesilate, canakinumab, convalescent plasma, dapagliflozin, dexamethasone, favipiravir, hydroxychloroquine, hydroxychloroquine plus azithromycin, hydroxychloroquine plus favipiravir, interferon beta, ivermectin, lopinavir/ritonavir, mesenchymal stem cells, remdesivir, sarilumab, tocilizumab, tofacitinib and SOC, which were investigated in 48 studies ( 3 , 6 , 22 – 26 , 31 , 43 , 46 , 55 , 57 , 64 , 71 – 73 , 76 , 80 , 82 , 84 , 89 , 91 , 93 , 96 – 98 , 100 , 101 , 106 , 107 , 109 , 110 , 115 , 116 , 121 , 122 , 124 , 126 , 128 – 132 , 145 – 147 , 157 , 158 ). Out of the 48 studies included in the NMA, 19 were evaluated as low risk ( Supplementary Table 7 ).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 45 studies including 6,631 patients reported viral clearance rates and after eliminating treatments with inadequate numbers of patients, 32 studies were considered in the NMA ( 36 , 53 , 54 , 56 , 57 , 59 , 65 , 68 , 71 , 72 , 76 , 78 , 80 , 91 , 106 , 109 , 119 , 132 , 136 , 137 , 141 , 153 , 157 – 166 ), of which 10 were assessed as low risk ( Supplementary Table 8 ). Treatment nodes in the network included bamlanivimab, bamlanivimab plus etesevimab, convalescent plasma, favipiravir, hydroxychloroquine, hydroxychloroquine plus azithromycin, hydroxychloroquine plus favipiravir, ivermectin, ivermectin plus doxycycline, lopinavir/ritonavir, methylprednisolone, nitazoxanide, proxalutamide, remdesivir and SOC.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Zhang

Jin

Wen

et al. 2021

Front. Public Health

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Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19).Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications.Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates.Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Zhang

Jin

Wen

et al. 2021

Front. Public Health

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“…Udwadia et al also concluded that the time to clinical cure was shorter in the treatment group than in the control group, suggesting that favipiravir might be beneficial in mild-to-moderate COVID-19 cases [ 9 ]. In the Fluids and Catheters Treatment Trial, the combination therapy of favipiravir and hydroxychloroquine did not show any clinical benefit in patients with moderate-to-severe COVID-19 [ 10 ]. A systematic review of such randomized controlled trials had suggested that favipiravir was only marginally effective [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan

et al. 2022

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Introduction Several randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient. Methods We used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, early-stage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a three-step method (cloning, censoring, and weighting). The primary outcome was supplementary oxygen requirement during hospitalization, and the secondary outcomes were the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO) and overall mortality at 30 days. Results A total of 7654 cases were analyzed. The “start favipiravir” regimen did not show substantial differences in the primary outcome [hazard ratio 0.825, 95% confidence interval (CI) 0.657–1.04, p = 0.098] and both of the secondary outcomes [need for IMV/ECMO and overall 30-day mortality, hazard ratio 1.02 (95% CI 0.649–1.60) and 0.869 (95% CI 0.519–1.46), p = 0.929 and 0.594, respectively]. Conclusions In this large cohort from a COVID-19 registry, favipiravir was not associated with a positive effect on the clinical outcome on patients with nonsevere, early-stage COVID-19, suggesting that it is not an essential drug for COVID-19 treatment.

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“…Our systematic literature search retrieved 1493 hits, of which 613 were unique. After screening, we included six randomized controlled trials ( Table 1 ) [1] , [2] , [3] , [4] , [5] , [6] , with a total of 1,669 patients with COVID-19. The meta-analysis of the included trials [1] , [2] , [3] , [4] , [5] , [6] revealed no significant difference in the odds of mortality with the use of favipiravir among patients with COVID-19, relative to non-use of favipiravir; the estimated effect though indicated increased mortality ( Figure 1 ; pooled odds ratio = 1.09; 95% confidence interval 0.76 to 1.56) but is without adequate evidence against the null hypothesis of ‘no significant difference,’ at the current sample size.…”

Section: Introductionmentioning

confidence: 99%

“…The meta-analysis of the included trials [1] , [2] , [3] , [4] , [5] , [6] revealed no significant difference in the odds of mortality with the use of favipiravir among patients with COVID-19, relative to non-use of favipiravir; the estimated effect though indicated increased mortality ( Figure 1 ; pooled odds ratio = 1.09; 95% confidence interval 0.76 to 1.56) but is without adequate evidence against the null hypothesis of ‘no significant difference,’ at the current sample size.…”

Section: Introductionmentioning

confidence: 99%

Future of antivirals in COVID-19: The case of favipiravir

Kow

Ramachandram

Hasan

2022

International Immunopharmacology

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Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial

Cited by 14 publications

References 26 publications

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan

Future of antivirals in COVID-19: The case of favipiravir

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