Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.
Identifieur interne : 000424 ( Main/Exploration ); précédent : 000423; suivant : 000425Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.
Auteurs : Petri J. Vainio [Finlande] ; Pauliina Hietasalo [Finlande] ; Anna-Liisa Koivisto [Finlande] ; Susanna K Ri Inen [Finlande] ; Jari Turunen [Finlande] ; Mika Virtala [Finlande] ; Jouni Vuorinen [Finlande] ; Mika Scheinin [Finlande]Source :
- Trials [ 1745-6215 ] ; 2021.
Descripteurs français
- KwdFr :
- Adolescent (MeSH), Adulte (MeSH), Adulte d'âge moyen (MeSH), Antienzymes (usage thérapeutique), Anxiété (psychologie), Cause de décès (MeSH), Comorbidité (MeSH), Diabète (épidémiologie), Essais contrôlés randomisés comme sujet (MeSH), Excrétion virale (MeSH), Facteurs temps (MeSH), Hospitalisation (statistiques et données numériques), Humains (MeSH), Hydroxychloroquine (usage thérapeutique), Indice de gravité de la maladie (MeSH), Jeune adulte (MeSH), Mortalité (MeSH), Méthode en double aveugle (MeSH), Obésité (épidémiologie), Résultat thérapeutique (MeSH), Soins ambulatoires (MeSH), Soins de santé primaires (MeSH), Sujet âgé (MeSH).
- MESH :
- psychologie : Anxiété.
- statistiques et données numériques : Hospitalisation.
- usage thérapeutique : Antienzymes, Hydroxychloroquine.
- épidémiologie : Diabète, Obésité.
- Adolescent, Adulte, Adulte d'âge moyen, Cause de décès, Comorbidité, Essais contrôlés randomisés comme sujet, Excrétion virale, Facteurs temps, Humains, Indice de gravité de la maladie, Jeune adulte, Mortalité, Méthode en double aveugle, Résultat thérapeutique, Soins ambulatoires, Soins de santé primaires, Sujet âgé.
English descriptors
- KwdEn :
- Adolescent (MeSH), Adult (MeSH), Aged (MeSH), Ambulatory Care (MeSH), Anxiety (psychology), COVID-19 (drug therapy), COVID-19 (epidemiology), COVID-19 (mortality), COVID-19 (psychology), Cause of Death (MeSH), Comorbidity (MeSH), Diabetes Mellitus (epidemiology), Double-Blind Method (MeSH), Enzyme Inhibitors (therapeutic use), Hospitalization (statistics & numerical data), Humans (MeSH), Hydroxychloroquine (therapeutic use), Middle Aged (MeSH), Mortality (MeSH), Obesity (epidemiology), Primary Health Care (MeSH), Randomized Controlled Trials as Topic (MeSH), SARS-CoV-2 (MeSH), Severity of Illness Index (MeSH), Time Factors (MeSH), Treatment Outcome (MeSH), Virus Shedding (MeSH), Young Adult (MeSH).
- MESH :
- chemical , therapeutic use : Enzyme Inhibitors, Hydroxychloroquine.
- drug therapy : COVID-19.
- epidemiology : COVID-19, Diabetes Mellitus, Obesity.
- mortality : COVID-19.
- psychology : Anxiety, COVID-19.
- statistics & numerical data : Hospitalization.
- Adolescent, Adult, Aged, Ambulatory Care, Cause of Death, Comorbidity, Double-Blind Method, Humans, Middle Aged, Mortality, Primary Health Care, Randomized Controlled Trials as Topic, SARS-CoV-2, Severity of Illness Index, Time Factors, Treatment Outcome, Virus Shedding, Young Adult.
Abstract
OBJECTIVES
The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis. The secondary objectives of the study are: to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo; to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; and to evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants. In addition, if the data allow, the study has the following exploratory objectives: to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo; to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo; to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo; to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population; to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications.
TRIAL DESIGN
This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms.
PARTICIPANTS
Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m
INTERVENTION AND COMPARATOR
Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days.
MAIN OUTCOMES
The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study. The secondary endpoints of the study include the following: duration and severity of Covid-19-related symptoms, as reported by daily self-assessments; number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study; number of deaths due to Covid-19 infection within four weeks of entry into the study; number of treatment-related adverse events (AEs) and serious AEs (SAEs); all-cause hospitalizations and mortality within six months of entry into the study; and self-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7). The exploratory endpoints of the study include the following: extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; and possible other blood biomarker changes.
RANDOMISATION
Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc™ (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study.
BLINDING (MASKING)
The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE)
600 participants are to be randomised with 300 in each arm.
TRIAL STATUS
Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021.
TRIAL REGISTRATION
EudraCT 2020-002038-33 , registered 26 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
DOI: 10.1186/s13063-020-04989-6
PubMed: 33430933
PubMed Central: PMC7797713
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.</title><author><name sortKey="Vainio, Petri J" sort="Vainio, Petri J" uniqKey="Vainio P" first="Petri J" last="Vainio">Petri J. Vainio</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Biomedicine, University of Turku, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedicine, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Clinical Pharmacology, Turku University Hospital, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Hietasalo, Pauliina" sort="Hietasalo, Pauliina" uniqKey="Hietasalo P" first="Pauliina" last="Hietasalo">Pauliina Hietasalo</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="Koivisto, Anna Liisa" sort="Koivisto, Anna Liisa" uniqKey="Koivisto A" first="Anna-Liisa" last="Koivisto">Anna-Liisa Koivisto</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="K Ri Inen, Susanna" sort="K Ri Inen, Susanna" uniqKey="K Ri Inen S" first="Susanna" last="K Ri Inen">Susanna K Ri Inen</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Clinical Research Services Turku - CRST Oy, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Turunen, Jari" sort="Turunen, Jari" uniqKey="Turunen J" first="Jari" last="Turunen">Jari Turunen</name><affiliation wicri:level="3"><nlm:affiliation>Oy 4Pharma Ltd., Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Oy 4Pharma Ltd., Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Virtala, Mika" sort="Virtala, Mika" uniqKey="Virtala M" first="Mika" last="Virtala">Mika Virtala</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="Vuorinen, Jouni" sort="Vuorinen, Jouni" uniqKey="Vuorinen J" first="Jouni" last="Vuorinen">Jouni Vuorinen</name><affiliation wicri:level="3"><nlm:affiliation>Oy 4Pharma Ltd., Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Oy 4Pharma Ltd., Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Scheinin, Mika" sort="Scheinin, Mika" uniqKey="Scheinin M" first="Mika" last="Scheinin">Mika Scheinin</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Biomedicine, University of Turku, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedicine, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Clinical Pharmacology, Turku University Hospital, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Clinical Research Services Turku - CRST Oy, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33430933</idno><idno type="pmid">33430933</idno><idno type="doi">10.1186/s13063-020-04989-6</idno><idno type="pmc">PMC7797713</idno><idno type="wicri:Area/Main/Corpus">000505</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000505</idno><idno type="wicri:Area/Main/Curation">000505</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000505</idno><idno type="wicri:Area/Main/Exploration">000505</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.</title><author><name sortKey="Vainio, Petri J" sort="Vainio, Petri J" uniqKey="Vainio P" first="Petri J" last="Vainio">Petri J. Vainio</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Biomedicine, University of Turku, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedicine, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Clinical Pharmacology, Turku University Hospital, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Hietasalo, Pauliina" sort="Hietasalo, Pauliina" uniqKey="Hietasalo P" first="Pauliina" last="Hietasalo">Pauliina Hietasalo</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="Koivisto, Anna Liisa" sort="Koivisto, Anna Liisa" uniqKey="Koivisto A" first="Anna-Liisa" last="Koivisto">Anna-Liisa Koivisto</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="K Ri Inen, Susanna" sort="K Ri Inen, Susanna" uniqKey="K Ri Inen S" first="Susanna" last="K Ri Inen">Susanna K Ri Inen</name><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Clinical Research Services Turku - CRST Oy, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Turunen, Jari" sort="Turunen, Jari" uniqKey="Turunen J" first="Jari" last="Turunen">Jari Turunen</name><affiliation wicri:level="3"><nlm:affiliation>Oy 4Pharma Ltd., Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Oy 4Pharma Ltd., Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Virtala, Mika" sort="Virtala, Mika" uniqKey="Virtala M" first="Mika" last="Virtala">Mika Virtala</name><affiliation wicri:level="1"><nlm:affiliation>Porin perusturva, Pori, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Porin perusturva, Pori</wicri:regionArea><wicri:noRegion>Pori</wicri:noRegion></affiliation></author><author><name sortKey="Vuorinen, Jouni" sort="Vuorinen, Jouni" uniqKey="Vuorinen J" first="Jouni" last="Vuorinen">Jouni Vuorinen</name><affiliation wicri:level="3"><nlm:affiliation>Oy 4Pharma Ltd., Turku, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Oy 4Pharma Ltd., Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Scheinin, Mika" sort="Scheinin, Mika" uniqKey="Scheinin M" first="Mika" last="Scheinin">Mika Scheinin</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Biomedicine, University of Turku, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedicine, University of Turku, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Clinical Pharmacology, Turku University Hospital, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland. mschein@utu.fi.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Clinical Research Services Turku - CRST Oy, Turku</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author></analytic><series><title level="j">Trials</title><idno type="eISSN">1745-6215</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Adult (MeSH)</term><term>Aged (MeSH)</term><term>Ambulatory Care (MeSH)</term><term>Anxiety (psychology)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (epidemiology)</term><term>COVID-19 (mortality)</term><term>COVID-19 (psychology)</term><term>Cause of Death (MeSH)</term><term>Comorbidity (MeSH)</term><term>Diabetes Mellitus (epidemiology)</term><term>Double-Blind Method (MeSH)</term><term>Enzyme Inhibitors (therapeutic use)</term><term>Hospitalization (statistics & numerical data)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Middle Aged (MeSH)</term><term>Mortality (MeSH)</term><term>Obesity (epidemiology)</term><term>Primary Health Care (MeSH)</term><term>Randomized Controlled Trials as Topic (MeSH)</term><term>SARS-CoV-2 (MeSH)</term><term>Severity of Illness Index (MeSH)</term><term>Time Factors (MeSH)</term><term>Treatment Outcome (MeSH)</term><term>Virus Shedding (MeSH)</term><term>Young Adult (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent (MeSH)</term><term>Adulte (MeSH)</term><term>Adulte d'âge moyen (MeSH)</term><term>Antienzymes (usage thérapeutique)</term><term>Anxiété (psychologie)</term><term>Cause de décès (MeSH)</term><term>Comorbidité (MeSH)</term><term>Diabète (épidémiologie)</term><term>Essais contrôlés randomisés comme sujet (MeSH)</term><term>Excrétion virale (MeSH)</term><term>Facteurs temps (MeSH)</term><term>Hospitalisation (statistiques et données numériques)</term><term>Humains (MeSH)</term><term>Hydroxychloroquine (usage thérapeutique)</term><term>Indice de gravité de la maladie (MeSH)</term><term>Jeune adulte (MeSH)</term><term>Mortalité (MeSH)</term><term>Méthode en double aveugle (MeSH)</term><term>Obésité (épidémiologie)</term><term>Résultat thérapeutique (MeSH)</term><term>Soins ambulatoires (MeSH)</term><term>Soins de santé primaires (MeSH)</term><term>Sujet âgé (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Enzyme Inhibitors</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term><term>Diabetes Mellitus</term><term>Obesity</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="psychologie" xml:lang="fr"><term>Anxiété</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Anxiety</term><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="statistics & numerical data" xml:lang="en"><term>Hospitalization</term></keywords><keywords scheme="MESH" qualifier="statistiques et données numériques" xml:lang="fr"><term>Hospitalisation</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antienzymes</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Diabète</term><term>Obésité</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Ambulatory Care</term><term>Cause of Death</term><term>Comorbidity</term><term>Double-Blind Method</term><term>Humans</term><term>Middle Aged</term><term>Mortality</term><term>Primary Health Care</term><term>Randomized Controlled Trials as Topic</term><term>SARS-CoV-2</term><term>Severity of Illness Index</term><term>Time Factors</term><term>Treatment Outcome</term><term>Virus Shedding</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Cause de décès</term><term>Comorbidité</term><term>Essais contrôlés randomisés comme sujet</term><term>Excrétion virale</term><term>Facteurs temps</term><term>Humains</term><term>Indice de gravité de la maladie</term><term>Jeune adulte</term><term>Mortalité</term><term>Méthode en double aveugle</term><term>Résultat thérapeutique</term><term>Soins ambulatoires</term><term>Soins de santé primaires</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVES</b></p><p>The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis. The secondary objectives of the study are: to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo; to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; and to evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants. In addition, if the data allow, the study has the following exploratory objectives: to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo; to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo; to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo; to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population; to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications.</p></div><div type="abstract" xml:lang="en"><p><b>TRIAL DESIGN</b></p><p>This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms.</p></div><div type="abstract" xml:lang="en"><p><b>PARTICIPANTS</b></p><p>Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m</p></div><div type="abstract" xml:lang="en"><p><b>INTERVENTION AND COMPARATOR</b></p><p>Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days.</p></div><div type="abstract" xml:lang="en"><p><b>MAIN OUTCOMES</b></p><p>The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study. The secondary endpoints of the study include the following: duration and severity of Covid-19-related symptoms, as reported by daily self-assessments; number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study; number of deaths due to Covid-19 infection within four weeks of entry into the study; number of treatment-related adverse events (AEs) and serious AEs (SAEs); all-cause hospitalizations and mortality within six months of entry into the study; and self-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7). The exploratory endpoints of the study include the following: extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; and possible other blood biomarker changes.</p></div><div type="abstract" xml:lang="en"><p><b>RANDOMISATION</b></p><p>Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc™ (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study.</p></div><div type="abstract" xml:lang="en"><p><b>BLINDING (MASKING)</b></p><p>The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance.</p></div><div type="abstract" xml:lang="en"><p><b>NUMBERS TO BE RANDOMISED (SAMPLE SIZE)</b></p><p>600 participants are to be randomised with 300 in each arm.</p></div><div type="abstract" xml:lang="en"><p><b>TRIAL STATUS</b></p><p>Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021.</p></div><div type="abstract" xml:lang="en"><p><b>TRIAL REGISTRATION</b></p><p>EudraCT 2020-002038-33 , registered 26 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33430933</PMID><DateCompleted><Year>2021</Year><Month>01</Month><Day>18</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>18</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1745-6215</ISSN><JournalIssue CitedMedium="Internet"><Volume>22</Volume><Issue>1</Issue><PubDate><Year>2021</Year><Month>Jan</Month><Day>11</Day></PubDate></JournalIssue><Title>Trials</Title><ISOAbbreviation>Trials</ISOAbbreviation></Journal><ArticleTitle>Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.</ArticleTitle><Pagination><MedlinePgn>44</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1186/s13063-020-04989-6</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis. The secondary objectives of the study are: to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo; to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; and to evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants. In addition, if the data allow, the study has the following exploratory objectives: to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo; to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo; to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo; to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population; to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications.</AbstractText><AbstractText Label="TRIAL DESIGN" NlmCategory="METHODS">This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms.</AbstractText><AbstractText Label="PARTICIPANTS" NlmCategory="METHODS">Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m<sup>2</sup>; 2. Valid independent informed consent obtained; 3. Symptoms typical of Covid-19 infection, according to criteria specified in the study protocol. The onset of symptoms must be within 5 days of enrolment; 4. Positive SARS-CoV-2 PCR test result of a nasopharyngeal swab sample. Main exclusion criteria: 1. Suspected severe or moderately severe pneumonia, presenting with any of the following: respiratory rate > 26 breaths/min; significant respiratory distress; or SpO<sub>2</sub> ≤94% on room air; 2. Requiring treatment in the hospital, according to the treating physician's judgement; 3. Any contraindication to treatment with HCQ; 4. Pregnancy or lactation. The trial will be conducted at seven study sites in a primary public health care setting in the region of Satakunta, Finland.</AbstractText><AbstractText Label="INTERVENTION AND COMPARATOR" NlmCategory="UNASSIGNED">Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days.</AbstractText><AbstractText Label="MAIN OUTCOMES" NlmCategory="RESULTS">The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study. The secondary endpoints of the study include the following: duration and severity of Covid-19-related symptoms, as reported by daily self-assessments; number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study; number of deaths due to Covid-19 infection within four weeks of entry into the study; number of treatment-related adverse events (AEs) and serious AEs (SAEs); all-cause hospitalizations and mortality within six months of entry into the study; and self-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7). The exploratory endpoints of the study include the following: extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; and possible other blood biomarker changes.</AbstractText><AbstractText Label="RANDOMISATION" NlmCategory="UNASSIGNED">Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc™ (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study.</AbstractText><AbstractText Label="BLINDING (MASKING)" NlmCategory="UNASSIGNED">The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance.</AbstractText><AbstractText Label="NUMBERS TO BE RANDOMISED (SAMPLE SIZE)" NlmCategory="UNASSIGNED">600 participants are to be randomised with 300 in each arm.</AbstractText><AbstractText Label="TRIAL STATUS" NlmCategory="UNASSIGNED">Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021.</AbstractText><AbstractText Label="TRIAL REGISTRATION" NlmCategory="BACKGROUND">EudraCT 2020-002038-33 , registered 26 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Vainio</LastName><ForeName>Petri J</ForeName><Initials>PJ</Initials><AffiliationInfo><Affiliation>Institute of Biomedicine, University of Turku, Turku, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hietasalo</LastName><ForeName>Pauliina</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Porin perusturva, Pori, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koivisto</LastName><ForeName>Anna-Liisa</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Porin perusturva, Pori, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kääriäinen</LastName><ForeName>Susanna</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Turunen</LastName><ForeName>Jari</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Oy 4Pharma Ltd., Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Virtala</LastName><ForeName>Mika</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Porin perusturva, Pori, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vuorinen</LastName><ForeName>Jouni</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Oy 4Pharma Ltd., Turku, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scheinin</LastName><ForeName>Mika</ForeName><Initials>M</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7579-9126</Identifier><AffiliationInfo><Affiliation>Institute of Biomedicine, University of Turku, Turku, Finland. mschein@utu.fi.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland. mschein@utu.fi.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Research Services Turku - CRST Oy, Turku, Finland. mschein@utu.fi.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D000078325">Clinical Trial Protocol</PublicationType><PublicationType UI="D016422">Letter</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Trials</MedlineTA><NlmUniqueID>101263253</NlmUniqueID><ISSNLinking>1745-6215</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004791">Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000553" MajorTopicYN="Y">Ambulatory Care</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001007" MajorTopicYN="N">Anxiety</DescriptorName><QualifierName UI="Q000523" MajorTopicYN="N">psychology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000523" MajorTopicYN="N">psychology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002423" MajorTopicYN="N">Cause of Death</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015897" MajorTopicYN="N">Comorbidity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003920" MajorTopicYN="N">Diabetes Mellitus</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004791" MajorTopicYN="N">Enzyme Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006760" MajorTopicYN="N">Hospitalization</DescriptorName><QualifierName UI="Q000706" MajorTopicYN="Y">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009026" MajorTopicYN="N">Mortality</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009765" MajorTopicYN="N">Obesity</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011320" MajorTopicYN="Y">Primary Health Care</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017201" MajorTopicYN="N">Virus Shedding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Randomised controlled trial</Keyword><Keyword MajorTopicYN="N">hospitalization</Keyword><Keyword MajorTopicYN="N">hydroxychloroquine</Keyword><Keyword MajorTopicYN="N">open care</Keyword><Keyword MajorTopicYN="N">primary care</Keyword><Keyword MajorTopicYN="N">protocol</Keyword><Keyword MajorTopicYN="N">public health care</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>12</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>12</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>1</Month><Day>12</Day><Hour>5</Hour><Minute>43</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>1</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33430933</ArticleId><ArticleId IdType="doi">10.1186/s13063-020-04989-6</ArticleId><ArticleId IdType="pii">10.1186/s13063-020-04989-6</ArticleId><ArticleId IdType="pmc">PMC7797713</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Finlande</li></country><region><li>Finlande occidentale</li></region><settlement><li>Turku</li></settlement><orgName><li>Université de Turku</li></orgName></list><tree><country name="Finlande"><region name="Finlande occidentale"><name sortKey="Vainio, Petri J" sort="Vainio, Petri J" uniqKey="Vainio P" first="Petri J" last="Vainio">Petri J. Vainio</name></region><name sortKey="Hietasalo, Pauliina" sort="Hietasalo, Pauliina" uniqKey="Hietasalo P" first="Pauliina" last="Hietasalo">Pauliina Hietasalo</name><name sortKey="K Ri Inen, Susanna" sort="K Ri Inen, Susanna" uniqKey="K Ri Inen S" first="Susanna" last="K Ri Inen">Susanna K Ri Inen</name><name sortKey="Koivisto, Anna Liisa" sort="Koivisto, Anna Liisa" uniqKey="Koivisto A" first="Anna-Liisa" last="Koivisto">Anna-Liisa Koivisto</name><name sortKey="Scheinin, Mika" sort="Scheinin, Mika" uniqKey="Scheinin M" first="Mika" last="Scheinin">Mika Scheinin</name><name sortKey="Scheinin, Mika" sort="Scheinin, Mika" uniqKey="Scheinin M" first="Mika" last="Scheinin">Mika Scheinin</name><name sortKey="Scheinin, Mika" sort="Scheinin, Mika" uniqKey="Scheinin M" first="Mika" last="Scheinin">Mika Scheinin</name><name sortKey="Turunen, Jari" sort="Turunen, Jari" uniqKey="Turunen J" first="Jari" last="Turunen">Jari Turunen</name><name sortKey="Vainio, Petri J" sort="Vainio, Petri J" uniqKey="Vainio P" first="Petri J" last="Vainio">Petri J. Vainio</name><name sortKey="Virtala, Mika" sort="Virtala, Mika" uniqKey="Virtala M" first="Mika" last="Virtala">Mika Virtala</name><name sortKey="Vuorinen, Jouni" sort="Vuorinen, Jouni" uniqKey="Vuorinen J" first="Jouni" last="Vuorinen">Jouni Vuorinen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000424 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000424 | 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:33430933
|texte= Hydroxychloroquine in the treatment of adult patients with Covid-19 infection in a primary care setting (LIBERTY): A structured summary of a study protocol for a randomised controlled trial.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:33430933" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |