Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Tang, Wei; Cao, Zhujun; Han, Mingyong; Wang, Zhengyan; Chen, Junwen; Sun, Weijian; Wu, Yaojie; Xiao, Wei; Liu, Shengyong; Chen, Erzhen; Chen, Wei; Wang, Xiongbiao; Yang, Jiuyong; Lin, Jie; Zhao, Quan; Yan, Youqin; Xie, Zhibin; Li, Dan; Yang, Yaofeng; Liu, Leshan; Qu, Jieming; Ning, Guang; Shi, Guochao; Xie, Qing

doi:10.1136/bmj.m1849

Cited by 889 publications

(1,072 citation statements)

References 18 publications

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“…<3 days or 3-7 days) contributed to shorter time to undetectable viral RNA by RT-PCR. In contrast, two recently reported RCTs on HCQ from Chen J et al and Tang W et al did not reveal a higher proportion of viral clearance in patients admitted to hospital with mainly mild to moderate COVID-19 than standard of care alone [8,22]. Our primary meta-analysis revealed a positive effect of HCQ/CQ on viral clearance by RT-PCR testing.…”

Section: Discussioncontrasting

confidence: 90%

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Chen

Yao

et al. 2020

Preprint

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Background: Hydroxychloroquine (HCQ) and chloroquine (CQ) have been widely used for the treatment of the coronavirus disease 2019 (COVID-19), despite limited clinical evidence and controversial early reports. The aim of this report was to provide a systematic review of the literature and meta-analysis on the use of HCQ/CQ with respect to safety and clinical efficacy of these medications. Methods: We performed a systematic search of the medical databases and included studies if they focused on patients with COVID-19 who received HCQ or CQ alone, or in combination with other treatments, and were compared with a control group. We analyzed two important clinical objectives; viral clearance rate by reverse transcription-polymerase chain reaction (RT-PCR) negativity and all-cause mortality.Results: A total of 14 studies were included in the quantitative synthesis. The use of HCQ/CQ was associated with higher viral clearance rate compared with control group (OR: 3.12, 95% CI: 2.17-4.49 p<0.0001). In the sensitivity analysis, the effect on viral clearance disappeared (OR 1.44, 95% CI: 0.87-2.37, p=0.155). The use of HCQ/CQ was associated with a higher risk of mortality (OR 1.26, 95% CI: 1.05-1.51, p<0.0001). Due to huge heterogeneity between the studies (I2 = 86%, p < 0.01), we performed a meta regression analysis. Both treatment within 24 hours (p=0.047) and comorbidities [hypertension (p=0.025), diabetes (p=0.049) and chronic lung disease (p=0.0064)] contributed to the heterogeneity. HCQ/CQ daily dose (p=0.61) and age (p=0.62) had no impact on effect size. Higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ. Overall, the use of HCQ/CQ resulted in longer QTc intervals.Conclusions: Our meta-analysis did not reveal a clinical benefit of HCQ/CQ on in-hospital outcomes for patients with COVID-19. The use of HCQ/CQ did not result in rapid viral clearance on RT-PCR. Moreover, our results showed that higher rate of comorbidities led to a higher risk of mortality by using HCQ/CQ.

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Section: Discussioncontrasting

confidence: 90%

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Chen

Yao

et al. 2020

Preprint

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“…Regular use of hydroxychloroquine was based on initial observational studies [16], but its e cacy was not con rmed in subsequent randomized controlled trials [4,17]. No recommendation prompted adjunctive treatments as no speci c treatment had been proven to decrease mortality of Covid-19…”

Section: Discussionmentioning

confidence: 99%

“…Data collection was performed by: Bernard Lambermont 1 , Marie Ernst 2 , Sandrine Boccar 4 The rst draft of the manuscript was written by Bernard Lambermont 1 and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript.…”

Section: Declarationsmentioning

confidence: 99%

“…However, evidence of the e cacy of such strategies is still lacking. Hydroxychloroquine was tested because of its capacity to increase endosomial pH and interfere with the glycosylation of cellular receptor of SARS-CoV-2 [2,3] but no clinical bene t could be shown in a randomized controlled trial [4]. The main hypothesis supporting the use of anti-in ammatory drugs is the concept of "cytokine storm", referring to an exacerbation of the host response mimicking what is observed after CAR-T cells administration for hematologic malignancies, and supposedly responsible for mortality of Covid-19 despite apparent clearance of the virus [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for mortality in a multicenter cohort of mechanically ventilated COVID-19 patients in Belgium.

Lambermont

Ernst

Demaret

et al. 2020

Preprint

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Background: Considering the high mortality rate of severe Covid-19 patients, it is necessary to identify prognostic factors and therapies which could be valuable in this setting.Methods: The method consisted in a multicentric retrospective analysis in all consecutive Covid-19 patients admitted to intensive care unit (ICU) and mechanically ventilated for more than 24 hours from March 1 to April 25, 2020.Admission date, age, sex, body mass index, underlying conditions, treatments, physiological values, use of vasopressors, renal replacement therapy and extracorporeal membrane oxygenation, duration of mechanical ventilation, length of ICU stay, ICU and ventilator-free days at day 42 were collected. Primary outcome was survival. Simple and multiple time-dependent Cox regression models were used to assess the effects of factors on survival. Results: Out of 2003 patients hospitalized for SARS-CoV-2, 361 were admitted to the participating ICUs, 257 were ventilated for more than 24 hours and 247 were included in the study. The length of stay in ICU was 21 (12-32) days and the mortality rate was 45%. Using multiple regression, risk factors for mortality were age, high serum creatinine value, low mean arterial pressure, low lymphocytes count on day 0 and the absence of corticosteroid therapy during the first week of mechanical ventilation. The mortality rate of the patients who received corticosteroids was 34% and 48% for patients who did not (p = 0.01).Conclusion: In this multicenter cohort, the mortality of patients with SARS-CoV-2 pneumonia treated with mechanical ventilation was high. The risk factors for mortality included age, renal and circulatory dysfunction, lymphopenia and the absence of corticosteroid therapy during the first week of mechanical ventilation.

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“…1 In a recent report, hydroxychloroquine given more than two weeks after rst symptoms had no effect on the clearance of SARS-CoV-2 in various respiratory tract specimens of afebrile patients hospitalized with coronavirus 2019 (COVID-19) partly pre-treated with antiviral drugs. 2 Viral clearance is however an incomplete characterization of viral kinetics, and the impact of hydroxychloroquine therapy on SARS-CoV-2 viral kinetics in subjects hospitalized with COVID-19 remains to be elucidated. Hydroxychloroquine is postulated to affect viral replication, and it is reasonable to assume that an effective antiviral drug will affect respiratory tract viral titers and thereby improve symptoms and host in ammatory responses, including the cytokine and chemokine expression that is likely responsible for many of the clinical symptoms of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

A pragmatic randomized controlled trial reports the efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics

Lyngbakken

Berdal

Eskesen

et al. 2020

Preprint

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We randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline of SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2.

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Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Abstract: OBJECTIVE To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19).

Cited by 889 publications

References 18 publications

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

Risk factors for mortality in a multicenter cohort of mechanically ventilated COVID-19 patients in Belgium.

A pragmatic randomized controlled trial reports the efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics

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