Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.
Mayla Gabriela Silva Borba,Fernando Fonseca Almeida Val,Vanderson de Souza Sampaio,Márcia A. A. Alexandre,Gisely Cardoso de Melo,Marcelo A M Brito,Maria Paula Gomes Mourão,Jose Diego Brito-Sousa,Djane Clarys Baia-da-Silva,Marcus Vinitius de Farias Guerra,Ludhmila Abrahão Hajjar,R. Pinto,Antônio Alcirley da Silva Balieiro,Antonio G. Pacheco,James D. Santos,Felipe Gomes Naveca,Mariana Simão Xavier,André M. Siqueira,Alexandre Vargas Schwarzbold,Julio Croda,Julio Croda,Maurício Lacerda Nogueira,Gustavo Adolfo Sierra Romero,Quique Bassat,Cor Jesus Fernandes Fontes,Bernardino Cláudio de Albuquerque,Cláudio Tadeu Daniel-Ribeiro,Wuelton Marcelo Monteiro,Marcus Lacerda +28 more
- Vol. 3, Iss: 4
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TLDR
The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir.Abstract:
Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04323527read more
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Remdesivir for the Treatment of Covid-19 - Final Report.
John H. Beigel,Kay M. Tomashek,Lori E. Dodd,Aneesh K. Mehta,Barry S. Zingman,Andre C. Kalil,Elizabeth L. Hohmann,Helen Y. Chu,Annie Luetkemeyer,Susan Kline,Diego Lopez de Castilla,Robert W. Finberg,Kerry Dierberg,Victor F. Tapson,Lanny Hsieh,Thomas F. Patterson,Roger Paredes,Daniel A. Sweeney,William R. Short,Giota Touloumi,David Chien Lye,Norio Ohmagari,Myoung-don Oh,Guillermo M. Ruiz-Palacios,Thomas Benfield,Gerd Fätkenheuer,Mark G. Kortepeter,Robert L. Atmar,C. Buddy Creech,JD Lundgren,Abdel G. Babiker,Sarah Pett,James D. Neaton,Timothy Burgess,Tyler Bonnett,Michelle Green,Mat Makowski,Anu Osinusi,Seema U Nayak,H. Clifford Lane +39 more
TL;DR: The data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection.
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
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Joshua Geleris,Yifei Sun,Jonathan Platt,Jason Zucker,Matthew R. Baldwin,George Hripcsak,Angelena Labella,Daniel K. Manson,Christine J. Kubin,R. Graham Barr,Magdalena E. Sobieszczyk,Neil W. Schluger +11 more
TL;DR: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.
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Nicolas Vabret,Graham J. Britton,Conor Gruber,Samarth Hegde,Joel Kim,Maria Kuksin,Rachel Levantovsky,Louise Malle,Alvaro Moreira,Matthew D. Park,Luisanna Pia,Emma Risson,Miriam Saffern,Bérengère Salomé,Myvizhi Esai Selvan,Matthew P. Spindler,Jessica Tan,Verena van der Heide,Jill Gregory,Konstantina Alexandropoulos,Nina Bhardwaj,Brian D. Brown,Benjamin Greenbaum,Zeynep H. Gümüş,Dirk Homann,Amir Horowitz,Alice O. Kamphorst,Maria A. Curotto de Lafaille,Saurabh Mehandru,Miriam Merad,Robert M. Samstein,Manasi Agrawal,Mark Aleynick,Meriem Belabed,Matthew Brown,Maria Casanova-Acebes,Jovani Catalan,Monica Centa,Andrew Charap,Andrew K Chan,Steven T. Chen,Jonathan Chung,Cansu Cimen Bozkus,Evan Cody,Francesca Cossarini,Erica Dalla,Nicolas F. Fernandez,John A. Grout,Dan Fu Ruan,Pauline Hamon,Etienne Humblin,Divya Jha,Julia Kodysh,Andrew Leader,Matthew Lin,Katherine E. Lindblad,Daniel Lozano-Ojalvo,Gabrielle Lubitz,Assaf Magen,Zafar Mahmood,Gustavo Martinez-Delgado,Jaime Mateus-Tique,Elliot Meritt,Chang Moon,Justine Noel,Timothy O'Donnell,Miyo Ota,Tamar Plitt,Venu Pothula,Jamie Redes,Ivan Reyes Torres,Mark P. Roberto,Alfonso R. Sanchez-Paulete,Joan Shang,Alessandra Soares Schanoski,Maria Suprun,Michelle Tran,Natalie Vaninov,C. Matthias Wilk,Julio A. Aguirre-Ghiso,Dusan Bogunovic,Judy H. Cho,Jeremiah J. Faith,Emilie K. Grasset,Peter S. Heeger,Ephraim Kenigsberg,Florian Krammer,Uri Laserson +87 more
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References
More filters
Journal ArticleDOI
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
Journal ArticleDOI
CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
TL;DR: The Consort 2010 Statement as discussed by the authors has been used worldwide to improve the reporting of randomised controlled trials and has been updated by Schulz et al. in 2010, based on new methodological evidence and accumulating experience.
Journal ArticleDOI
Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
Xiaobo Yang,Yuan Yu,Jiqian Xu,Huaqing Shu,Jia'an Xia,Hong Liu,Hong Liu,Yongran Wu,Lu Zhang,Zhui Yu,Minghao Fang,Ting Yu,Yaxin Wang,Shangwen Pan,Xiaojing Zou,Shiying Yuan,You Shang,You Shang +17 more
TL;DR: The clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital between late December, 2019 and Jan 26, 2020 are described.
Journal ArticleDOI
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
Manli Wang,Ruiyuan Cao,Leike Zhang,Xing-Lou Yang,Jia Liu,Mingyue Xu,Zhengli Shi,Zhihong Hu,Wu Zhong,Gengfu Xiao +9 more
TL;DR: This study evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir and favipiravir against a clinical isolate of 2019-nCoV in vitro.
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