CovidChloroV1, Main, Exploration, bibRecord, 000D68

Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

Identifieur interne : 000D68 ( Main/Exploration ); précédent : 000D67; suivant : 000D69

Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

Auteurs : Jonathan D. Casey ; Nicholas J. Johnson ; Matthew W. Semler ; Sean P. Collins ; Neil R. Aggarwal [États-Unis] ; Roy G. Brower [États-Unis] ; Steven Y. Chang [États-Unis] ; John Eppensteiner [États-Unis] ; Michael Filbin ; Kevin W. Gibbs [États-Unis] ; Adit A. Ginde ; Michelle N. Gong [États-Unis] ; Frank Harrell [États-Unis] ; Douglas L. Hayden ; Catherine L. Hough ; Akram Khan [États-Unis] ; Lindsay M. Leither [États-Unis] ; Marc Moss [États-Unis] ; Cathryn F. Oldmixon ; Pauline K. Park [États-Unis] ; Lora A. Reineck [États-Unis] ; Nancy J. Ringwood ; Bryce R H. Robinson [États-Unis] ; David A. Schoenfeld ; Nathan I. Shapiro [États-Unis] ; Jay S. Steingrub [États-Unis] ; Donna K. Torr ; Alexandra Weissman [États-Unis] ; Christopher J. Lindsell [États-Unis] ; Todd W. Rice ; B Taylor Thompson [États-Unis] ; Samuel M. Brown [États-Unis] ; Wesley H. Self

Source :

Annals of the American Thoracic Society [ 2325-6621 ] ; 2020.

RBID : pubmed:32492354

Descripteurs français

KwdFr :
- Adulte (MeSH), Antipaludiques (administration et posologie), Betacoronavirus (MeSH), Hospitalisation (tendances), Humains (MeSH), Hydroxychloroquine (administration et posologie), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (épidémiologie), Méthode en simple aveugle (MeSH), Pandémies (MeSH), Pneumopathie virale (traitement médicamenteux), Pneumopathie virale (épidémiologie), Relation dose-effet des médicaments (MeSH), Résultat thérapeutique (MeSH).
MESH :
- administration et posologie : Antipaludiques, Hydroxychloroquine.
- tendances : Hospitalisation.
- traitement médicamenteux : Infections à coronavirus, Pneumopathie virale.
- épidémiologie : Infections à coronavirus, Pneumopathie virale.
- Adulte, Betacoronavirus, Humains, Méthode en simple aveugle, Pandémies, Relation dose-effet des médicaments, Résultat thérapeutique.

English descriptors

KwdEn :
- Adult (MeSH), Antimalarials (administration & dosage), Betacoronavirus (MeSH), COVID-19 (MeSH), Coronavirus Infections (drug therapy), Coronavirus Infections (epidemiology), Dose-Response Relationship, Drug (MeSH), Hospitalization (trends), Humans (MeSH), Hydroxychloroquine (administration & dosage), Pandemics (MeSH), Pneumonia, Viral (drug therapy), Pneumonia, Viral (epidemiology), SARS-CoV-2 (MeSH), Single-Blind Method (MeSH), Treatment Outcome (MeSH).
MESH :
- chemical , administration & dosage : Antimalarials, Hydroxychloroquine.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- epidemiology : Coronavirus Infections, Pneumonia, Viral.
- trends : Hospitalization.
- Adult, Betacoronavirus, COVID-19, Dose-Response Relationship, Drug, Humans, Pandemics, SARS-CoV-2, Single-Blind Method, Treatment Outcome.

Abstract

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).

DOI: 10.1513/AnnalsATS.202005-478SD
PubMed: 32492354
PubMed Central: PMC7462324

Affiliations:

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Le document en format XML

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<author><name sortKey="Shapiro, Nathan I" sort="Shapiro, Nathan I" uniqKey="Shapiro N" first="Nathan I" last="Shapiro">Nathan I. Shapiro</name>
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<author><name sortKey="Steingrub, Jay S" sort="Steingrub, Jay S" uniqKey="Steingrub J" first="Jay S" last="Steingrub">Jay S. Steingrub</name>
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<author><name sortKey="Torr, Donna K" sort="Torr, Donna K" uniqKey="Torr D" first="Donna K" last="Torr">Donna K. Torr</name>
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</affiliation>
</author>
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<author><name sortKey="Lindsell, Christopher J" sort="Lindsell, Christopher J" uniqKey="Lindsell C" first="Christopher J" last="Lindsell">Christopher J. Lindsell</name>
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</placeName>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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<author><name sortKey="Brown, Samuel M" sort="Brown, Samuel M" uniqKey="Brown S" first="Samuel M" last="Brown">Samuel M. Brown</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.</title>
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</affiliation>
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<author><name sortKey="Collins, Sean P" sort="Collins, Sean P" uniqKey="Collins S" first="Sean P" last="Collins">Sean P. Collins</name>
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<wicri:noCountry code="subField">and</wicri:noCountry>
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<author><name sortKey="Aggarwal, Neil R" sort="Aggarwal, Neil R" uniqKey="Aggarwal N" first="Neil R" last="Aggarwal">Neil R. Aggarwal</name>
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<author><name sortKey="Chang, Steven Y" sort="Chang, Steven Y" uniqKey="Chang S" first="Steven Y" last="Chang">Steven Y. Chang</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Division of Pulmonary and Critical Care Medicine, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Eppensteiner, John" sort="Eppensteiner, John" uniqKey="Eppensteiner J" first="John" last="Eppensteiner">John Eppensteiner</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, Duke University, Durham, North Carolina.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Department of Surgery, Duke University, Durham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Filbin, Michael" sort="Filbin, Michael" uniqKey="Filbin M" first="Michael" last="Filbin">Michael Filbin</name>
<affiliation><nlm:affiliation>Department of Emergency Medicine.</nlm:affiliation>
<wicri:noCountry code="no comma">Department of Emergency Medicine.</wicri:noCountry>
<wicri:noCountry code="no comma">Department of Emergency Medicine.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gibbs, Kevin W" sort="Gibbs, Kevin W" uniqKey="Gibbs K" first="Kevin W" last="Gibbs">Kevin W. Gibbs</name>
<affiliation wicri:level="2"><nlm:affiliation>Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
<wicri:cityArea>Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Department of Medicine, Wake Forest School of Medicine, Winston-Salem</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ginde, Adit A" sort="Ginde, Adit A" uniqKey="Ginde A" first="Adit A" last="Ginde">Adit A. Ginde</name>
<affiliation><nlm:affiliation>Department of Emergency Medicine and.</nlm:affiliation>
<wicri:noCountry code="no comma">Department of Emergency Medicine and.</wicri:noCountry>
<wicri:noCountry code="no comma">Department of Emergency Medicine and.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gong, Michelle N" sort="Gong, Michelle N" uniqKey="Gong M" first="Michelle N" last="Gong">Michelle N. Gong</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Epidemiology and Population Health, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, New York.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Division of Epidemiology and Population Health, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New York City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Harrell, Frank" sort="Harrell, Frank" uniqKey="Harrell F" first="Frank" last="Harrell">Frank Harrell</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Biostatistics, Vanderbilt University School of Medicine, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hayden, Douglas L" sort="Hayden, Douglas L" uniqKey="Hayden D" first="Douglas L" last="Hayden">Douglas L. Hayden</name>
<affiliation><nlm:affiliation>Department of Medicine, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hough, Catherine L" sort="Hough, Catherine L" uniqKey="Hough C" first="Catherine L" last="Hough">Catherine L. Hough</name>
<affiliation><nlm:affiliation>Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Khan, Akram" sort="Khan, Akram" uniqKey="Khan A" first="Akram" last="Khan">Akram Khan</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University School of Medicine, Portland, Oregon.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Oregon</region>
</placeName>
<wicri:cityArea>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University School of Medicine, Portland</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Leither, Lindsay M" sort="Leither, Lindsay M" uniqKey="Leither L" first="Lindsay M" last="Leither">Lindsay M. Leither</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah, Salt Lake City, Utah.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Moss, Marc" sort="Moss, Marc" uniqKey="Moss M" first="Marc" last="Moss">Marc Moss</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, Colorado.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
<wicri:cityArea>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Oldmixon, Cathryn F" sort="Oldmixon, Cathryn F" uniqKey="Oldmixon C" first="Cathryn F" last="Oldmixon">Cathryn F. Oldmixon</name>
<affiliation><nlm:affiliation>Department of Medicine, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Park, Pauline K" sort="Park, Pauline K" uniqKey="Park P" first="Pauline K" last="Park">Pauline K. Park</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, University of Michigan, Ann Arbor, Michigan.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Michigan</region>
</placeName>
<wicri:cityArea>Department of Surgery, University of Michigan, Ann Arbor</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Reineck, Lora A" sort="Reineck, Lora A" uniqKey="Reineck L" first="Lora A" last="Reineck">Lora A. Reineck</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Lung Diseases, National Heart, Lung and Blood Institute, Bethesda, Maryland.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Division of Lung Diseases, National Heart, Lung and Blood Institute, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ringwood, Nancy J" sort="Ringwood, Nancy J" uniqKey="Ringwood N" first="Nancy J" last="Ringwood">Nancy J. Ringwood</name>
<affiliation><nlm:affiliation>Department of Medicine, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Robinson, Bryce R H" sort="Robinson, Bryce R H" uniqKey="Robinson B" first="Bryce R H" last="Robinson">Bryce R H. Robinson</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Surgery, University of Washington, Seattle, Washington.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<wicri:cityArea>Department of Surgery, University of Washington, Seattle</wicri:cityArea>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Schoenfeld, David A" sort="Schoenfeld, David A" uniqKey="Schoenfeld D" first="David A" last="Schoenfeld">David A. Schoenfeld</name>
<affiliation><nlm:affiliation>Department of Medicine, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Shapiro, Nathan I" sort="Shapiro, Nathan I" uniqKey="Shapiro N" first="Nathan I" last="Shapiro">Nathan I. Shapiro</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Steingrub, Jay S" sort="Steingrub, Jay S" uniqKey="Steingrub J" first="Jay S" last="Steingrub">Jay S. Steingrub</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, University of Massachusetts Medical School-Baystate, Springfield, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Medicine, University of Massachusetts Medical School-Baystate, Springfield</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Torr, Donna K" sort="Torr, Donna K" uniqKey="Torr D" first="Donna K" last="Torr">Donna K. Torr</name>
<affiliation><nlm:affiliation>Department of Pharmacy Services, Vanderbilt University Medical Center, Nashville, Tennessee; and.</nlm:affiliation>
<wicri:noCountry code="subField">Tennessee; and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Weissman, Alexandra" sort="Weissman, Alexandra" uniqKey="Weissman A" first="Alexandra" last="Weissman">Alexandra Weissman</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<wicri:cityArea>Department of Emergency Medicine, University of Pittsburgh, Pittsburgh</wicri:cityArea>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Lindsell, Christopher J" sort="Lindsell, Christopher J" uniqKey="Lindsell C" first="Christopher J" last="Lindsell">Christopher J. Lindsell</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Biostatistics, Vanderbilt University School of Medicine, Nashville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Rice, Todd W" sort="Rice, Todd W" uniqKey="Rice T" first="Todd W" last="Rice">Todd W. Rice</name>
<affiliation><nlm:affiliation>Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.</nlm:affiliation>
<wicri:noCountry code="subField">Department of Medicine</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Thompson, B Taylor" sort="Thompson, B Taylor" uniqKey="Thompson B" first="B Taylor" last="Thompson">B Taylor Thompson</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Brown, Samuel M" sort="Brown, Samuel M" uniqKey="Brown S" first="Samuel M" last="Brown">Samuel M. Brown</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah, Salt Lake City, Utah.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Self, Wesley H" sort="Self, Wesley H" uniqKey="Self W" first="Wesley H" last="Self">Wesley H. Self</name>
<affiliation><nlm:affiliation>Department of Emergency Medicine, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Annals of the American Thoracic Society</title>
<idno type="eISSN">2325-6621</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Antimalarials (administration & dosage)</term>
<term>Betacoronavirus (MeSH)</term>
<term>COVID-19 (MeSH)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (epidemiology)</term>
<term>Dose-Response Relationship, Drug (MeSH)</term>
<term>Hospitalization (trends)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (administration & dosage)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (drug therapy)</term>
<term>Pneumonia, Viral (epidemiology)</term>
<term>SARS-CoV-2 (MeSH)</term>
<term>Single-Blind Method (MeSH)</term>
<term>Treatment Outcome (MeSH)</term>
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<term>Antipaludiques (administration et posologie)</term>
<term>Betacoronavirus (MeSH)</term>
<term>Hospitalisation (tendances)</term>
<term>Humains (MeSH)</term>
<term>Hydroxychloroquine (administration et posologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Infections à coronavirus (épidémiologie)</term>
<term>Méthode en simple aveugle (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (traitement médicamenteux)</term>
<term>Pneumopathie virale (épidémiologie)</term>
<term>Relation dose-effet des médicaments (MeSH)</term>
<term>Résultat thérapeutique (MeSH)</term>
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<term>Hydroxychloroquine</term>
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<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
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<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="tendances" xml:lang="fr"><term>Hospitalisation</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
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<keywords scheme="MESH" qualifier="trends" xml:lang="en"><term>Hospitalization</term>
</keywords>
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<term>Pneumopathie virale</term>
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<term>COVID-19</term>
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<term>Pandemics</term>
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<front><div type="abstract" xml:lang="en">The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including <i>1</i>
) widespread, off-label use of the study drug before the availability of safety and efficacy data; <i>2</i>
) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; <i>3</i>
) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; <i>4</i>
) obtaining indistinguishable drug and placebo without delaying enrollment; and <i>5</i>
) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32492354</PMID>
<DateCompleted><Year>2020</Year>
<Month>09</Month>
<Day>21</Day>
</DateCompleted>
<DateRevised><Year>2021</Year>
<Month>05</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2325-6621</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>17</Volume>
<Issue>9</Issue>
<PubDate><Year>2020</Year>
<Month>09</Month>
</PubDate>
</JournalIssue>
<Title>Annals of the American Thoracic Society</Title>
<ISOAbbreviation>Ann Am Thorac Soc</ISOAbbreviation>
</Journal>
<ArticleTitle>Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.</ArticleTitle>
<Pagination><MedlinePgn>1144-1153</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1513/AnnalsATS.202005-478SD</ELocationID>
<Abstract><AbstractText>The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including <i>1</i>
) widespread, off-label use of the study drug before the availability of safety and efficacy data; <i>2</i>
) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; <i>3</i>
) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; <i>4</i>
) obtaining indistinguishable drug and placebo without delaying enrollment; and <i>5</i>
) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Casey</LastName>
<ForeName>Jonathan D</ForeName>
<Initials>JD</Initials>
<Identifier Source="ORCID">0000-0002-0977-290X</Identifier>
<AffiliationInfo><Affiliation>Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Johnson</LastName>
<ForeName>Nicholas J</ForeName>
<Initials>NJ</Initials>
<Identifier Source="ORCID">0000-0001-9915-0591</Identifier>
<AffiliationInfo><Affiliation>Department of Emergency Medicine.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Semler</LastName>
<ForeName>Matthew W</ForeName>
<Initials>MW</Initials>
<Identifier Source="ORCID">0000-0002-7664-8263</Identifier>
<AffiliationInfo><Affiliation>Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Collins</LastName>
<ForeName>Sean P</ForeName>
<Initials>SP</Initials>
<AffiliationInfo><Affiliation>Department of Emergency Medicine, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aggarwal</LastName>
<ForeName>Neil R</ForeName>
<Initials>NR</Initials>
<AffiliationInfo><Affiliation>Division of Lung Diseases, National Heart, Lung and Blood Institute, Bethesda, Maryland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brower</LastName>
<ForeName>Roy G</ForeName>
<Initials>RG</Initials>
<AffiliationInfo><Affiliation>Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chang</LastName>
<ForeName>Steven Y</ForeName>
<Initials>SY</Initials>
<AffiliationInfo><Affiliation>Division of Pulmonary and Critical Care Medicine, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, California.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Eppensteiner</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Surgery, Duke University, Durham, North Carolina.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Filbin</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Emergency Medicine.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gibbs</LastName>
<ForeName>Kevin W</ForeName>
<Initials>KW</Initials>
<AffiliationInfo><Affiliation>Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ginde</LastName>
<ForeName>Adit A</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>Department of Emergency Medicine and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gong</LastName>
<ForeName>Michelle N</ForeName>
<Initials>MN</Initials>
<AffiliationInfo><Affiliation>Division of Epidemiology and Population Health, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, New York.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Harrell</LastName>
<ForeName>Frank</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hayden</LastName>
<ForeName>Douglas L</ForeName>
<Initials>DL</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hough</LastName>
<ForeName>Catherine L</ForeName>
<Initials>CL</Initials>
<AffiliationInfo><Affiliation>Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Khan</LastName>
<ForeName>Akram</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University School of Medicine, Portland, Oregon.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leither</LastName>
<ForeName>Lindsay M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah, Salt Lake City, Utah.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Moss</LastName>
<ForeName>Marc</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, Colorado.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oldmixon</LastName>
<ForeName>Cathryn F</ForeName>
<Initials>CF</Initials>
<AffiliationInfo><Affiliation>Department of Medicine, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Park</LastName>
<ForeName>Pauline K</ForeName>
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Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000D68 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000D68 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    CovidChloroV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:32492354
   |texte=   Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:32492354" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a CovidChloroV1

This area was generated with Dilib version V0.6.38.
Data generation: Sat May 22 17:02:32 2021. Site generation: Sat May 22 17:06:52 2021

	Serveur d'exploration COVID et hydrochloroquine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration COVID et hydrochloroquine

Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

Rationale and Design of ORCHID: A Randomized Placebo-controlled Clinical Trial of Hydroxychloroquine for Adults Hospitalized with COVID-19.

Source :

Descripteurs français

English descriptors

Abstract

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Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki