Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
Identifieur interne : 000086 ( Main/Exploration ); précédent : 000085; suivant : 000087Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
Auteurs : Jordana B. Cohen [États-Unis] ; Thomas C. Hanff [États-Unis] ; Preethi William [États-Unis] ; Nancy Sweitzer [États-Unis] ; Nelson R. Rosado-Santander [Pérou] ; Carola Medina [Pérou] ; Juan E. Rodriguez-Mori [Pérou] ; Nicolás Renna [Argentine] ; Tara I. Chang [États-Unis] ; Vicente Corrales-Medina [Canada] ; Jaime F. Andrade-Villanueva [Mexique] ; Alejandro Barbagelata [États-Unis] ; Roberto Cristodulo-Cortez ; Omar A. Díaz-Cucho [Pérou] ; Jonas Spaak [Suède] ; Carlos E. Alfonso [États-Unis] ; Renzo Valdivia-Vega [Pérou] ; Mirko Villavicencio-Carranza [Pérou] ; Ricardo J. Ayala-García [Pérou] ; Carlos A. Castro-Callirgos [Pérou] ; Luz A. González-Hernández [Mexique] ; Eduardo F. Bernales-Salas [Pérou] ; Johanna C. Coacalla-Guerra [Pérou] ; Cynthia D. Salinas-Herrera [Pérou] ; Liliana Nicolosi [Argentine] ; Mauro Basconcel [Argentine] ; James B. Byrd [États-Unis] ; Tiffany Sharkoski [États-Unis] ; Luis E. Bendezú-Huasasquiche [Pérou] ; Jesse Chittams [États-Unis] ; Daniel L. Edmonston [États-Unis] ; Charles R. Vasquez [États-Unis] ; Julio A. Chirinos [États-Unis]Source :
- The Lancet. Respiratory medicine [ 2213-2619 ] ; 2021.
Abstract
BACKGROUND
Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
METHODS
The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.
FINDINGS
Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m
INTERPRETATION
Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.
FUNDING
REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.
DOI: 10.1016/S2213-2600(20)30558-0
PubMed: 33422263
PubMed Central: PMC7832152
Affiliations:
- Argentine, Canada, Mexique, Pérou, Suède, États-Unis
- Arizona, Californie, Caroline du Nord, Floride, Michigan, Pennsylvanie, Svealand
- Stockholm
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Cohen</name><affiliation wicri:level="2"><nlm:affiliation>Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Hanff, Thomas C" sort="Hanff, Thomas C" uniqKey="Hanff T" first="Thomas C" last="Hanff">Thomas C. 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Rodriguez-Mori</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Renna, Nicolas" sort="Renna, Nicolas" uniqKey="Renna N" first="Nicolás" last="Renna">Nicolás Renna</name><affiliation wicri:level="1"><nlm:affiliation>Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza</wicri:regionArea><wicri:noRegion>Mendoza</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Tara I" sort="Chang, Tara I" uniqKey="Chang T" first="Tara I" last="Chang">Tara I. Chang</name><affiliation wicri:level="2"><nlm:affiliation>Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Corrales Medina, Vicente" sort="Corrales Medina, Vicente" uniqKey="Corrales Medina V" first="Vicente" last="Corrales-Medina">Vicente Corrales-Medina</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Andrade Villanueva, Jaime F" sort="Andrade Villanueva, Jaime F" uniqKey="Andrade Villanueva J" first="Jaime F" last="Andrade-Villanueva">Jaime F. Andrade-Villanueva</name><affiliation wicri:level="1"><nlm:affiliation>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara</wicri:regionArea><wicri:noRegion>Guadalajara</wicri:noRegion></affiliation></author><author><name sortKey="Barbagelata, Alejandro" sort="Barbagelata, Alejandro" uniqKey="Barbagelata A" first="Alejandro" last="Barbagelata">Alejandro Barbagelata</name><affiliation wicri:level="2"><nlm:affiliation>Universidad Católica de Buenos Aires, Buenos Aires, Argentina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Universidad Católica de Buenos Aires, Buenos Aires, Argentina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Cristodulo Cortez, Roberto" sort="Cristodulo Cortez, Roberto" uniqKey="Cristodulo Cortez R" first="Roberto" last="Cristodulo-Cortez">Roberto Cristodulo-Cortez</name><affiliation><nlm:affiliation>Departamento de Medicina Interna, Hospital Obrero number 3 Caja Nacional de Salud, Santa Cruz de la Sierra, Bolivia.</nlm:affiliation><wicri:noCountry code="subField">Bolivia</wicri:noCountry></affiliation></author><author><name sortKey="Diaz Cucho, Omar A" sort="Diaz Cucho, Omar A" uniqKey="Diaz Cucho O" first="Omar A" last="Díaz-Cucho">Omar A. Díaz-Cucho</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao</wicri:regionArea><wicri:noRegion>Callao</wicri:noRegion></affiliation></author><author><name sortKey="Spaak, Jonas" sort="Spaak, Jonas" uniqKey="Spaak J" first="Jonas" last="Spaak">Jonas Spaak</name><affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Alfonso, Carlos E" sort="Alfonso, Carlos E" uniqKey="Alfonso C" first="Carlos E" last="Alfonso">Carlos E. Alfonso</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Valdivia Vega, Renzo" sort="Valdivia Vega, Renzo" uniqKey="Valdivia Vega R" first="Renzo" last="Valdivia-Vega">Renzo Valdivia-Vega</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Villavicencio Carranza, Mirko" sort="Villavicencio Carranza, Mirko" uniqKey="Villavicencio Carranza M" first="Mirko" last="Villavicencio-Carranza">Mirko Villavicencio-Carranza</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Ayala Garcia, Ricardo J" sort="Ayala Garcia, Ricardo J" uniqKey="Ayala Garcia R" first="Ricardo J" last="Ayala-García">Ricardo J. Ayala-García</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Castro Callirgos, Carlos A" sort="Castro Callirgos, Carlos A" uniqKey="Castro Callirgos C" first="Carlos A" last="Castro-Callirgos">Carlos A. Castro-Callirgos</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Gonzalez Hernandez, Luz A" sort="Gonzalez Hernandez, Luz A" uniqKey="Gonzalez Hernandez L" first="Luz A" last="González-Hernández">Luz A. González-Hernández</name><affiliation wicri:level="1"><nlm:affiliation>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara</wicri:regionArea><wicri:noRegion>Guadalajara</wicri:noRegion></affiliation></author><author><name sortKey="Bernales Salas, Eduardo F" sort="Bernales Salas, Eduardo F" uniqKey="Bernales Salas E" first="Eduardo F" last="Bernales-Salas">Eduardo F. Bernales-Salas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Coacalla Guerra, Johanna C" sort="Coacalla Guerra, Johanna C" uniqKey="Coacalla Guerra J" first="Johanna C" last="Coacalla-Guerra">Johanna C. Coacalla-Guerra</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Salinas Herrera, Cynthia D" sort="Salinas Herrera, Cynthia D" uniqKey="Salinas Herrera C" first="Cynthia D" last="Salinas-Herrera">Cynthia D. Salinas-Herrera</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Nicolosi, Liliana" sort="Nicolosi, Liliana" uniqKey="Nicolosi L" first="Liliana" last="Nicolosi">Liliana Nicolosi</name><affiliation wicri:level="1"><nlm:affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Basconcel, Mauro" sort="Basconcel, Mauro" uniqKey="Basconcel M" first="Mauro" last="Basconcel">Mauro Basconcel</name><affiliation wicri:level="1"><nlm:affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Byrd, James B" sort="Byrd, James B" uniqKey="Byrd J" first="James B" last="Byrd">James B. Byrd</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Sharkoski, Tiffany" sort="Sharkoski, Tiffany" uniqKey="Sharkoski T" first="Tiffany" last="Sharkoski">Tiffany Sharkoski</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Bendezu Huasasquiche, Luis E" sort="Bendezu Huasasquiche, Luis E" uniqKey="Bendezu Huasasquiche L" first="Luis E" last="Bendezú-Huasasquiche">Luis E. Bendezú-Huasasquiche</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao</wicri:regionArea><wicri:noRegion>Callao</wicri:noRegion></affiliation></author><author><name sortKey="Chittams, Jesse" sort="Chittams, Jesse" uniqKey="Chittams J" first="Jesse" last="Chittams">Jesse Chittams</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Edmonston, Daniel L" sort="Edmonston, Daniel L" uniqKey="Edmonston D" first="Daniel L" last="Edmonston">Daniel L. Edmonston</name><affiliation wicri:level="2"><nlm:affiliation>Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Vasquez, Charles R" sort="Vasquez, Charles R" uniqKey="Vasquez C" first="Charles R" last="Vasquez">Charles R. Vasquez</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Chirinos, Julio A" sort="Chirinos, Julio A" uniqKey="Chirinos J" first="Julio A" last="Chirinos">Julio A. Chirinos</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: julio.chirinos@uphs.upenn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33422263</idno><idno type="pmid">33422263</idno><idno type="doi">10.1016/S2213-2600(20)30558-0</idno><idno type="pmc">PMC7832152</idno><idno type="wicri:Area/Main/Corpus">000054</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000054</idno><idno type="wicri:Area/Main/Curation">000054</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000054</idno><idno type="wicri:Area/Main/Exploration">000054</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.</title><author><name sortKey="Cohen, Jordana B" sort="Cohen, Jordana B" uniqKey="Cohen J" first="Jordana B" last="Cohen">Jordana B. Cohen</name><affiliation wicri:level="2"><nlm:affiliation>Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Hanff, Thomas C" sort="Hanff, Thomas C" uniqKey="Hanff T" first="Thomas C" last="Hanff">Thomas C. Hanff</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="William, Preethi" sort="William, Preethi" uniqKey="William P" first="Preethi" last="William">Preethi William</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiology, University of Arizona, Tucson, AZ, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiology, University of Arizona, Tucson, AZ</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Sweitzer, Nancy" sort="Sweitzer, Nancy" uniqKey="Sweitzer N" first="Nancy" last="Sweitzer">Nancy Sweitzer</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiology, University of Arizona, Tucson, AZ, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiology, University of Arizona, Tucson, AZ</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Rosado Santander, Nelson R" sort="Rosado Santander, Nelson R" uniqKey="Rosado Santander N" first="Nelson R" last="Rosado-Santander">Nelson R. Rosado-Santander</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Medina, Carola" sort="Medina, Carola" uniqKey="Medina C" first="Carola" last="Medina">Carola Medina</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Rodriguez Mori, Juan E" sort="Rodriguez Mori, Juan E" uniqKey="Rodriguez Mori J" first="Juan E" last="Rodriguez-Mori">Juan E. Rodriguez-Mori</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Renna, Nicolas" sort="Renna, Nicolas" uniqKey="Renna N" first="Nicolás" last="Renna">Nicolás Renna</name><affiliation wicri:level="1"><nlm:affiliation>Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza</wicri:regionArea><wicri:noRegion>Mendoza</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Tara I" sort="Chang, Tara I" uniqKey="Chang T" first="Tara I" last="Chang">Tara I. Chang</name><affiliation wicri:level="2"><nlm:affiliation>Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology, Stanford University School of Medicine, Stanford, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Corrales Medina, Vicente" sort="Corrales Medina, Vicente" uniqKey="Corrales Medina V" first="Vicente" last="Corrales-Medina">Vicente Corrales-Medina</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Andrade Villanueva, Jaime F" sort="Andrade Villanueva, Jaime F" uniqKey="Andrade Villanueva J" first="Jaime F" last="Andrade-Villanueva">Jaime F. Andrade-Villanueva</name><affiliation wicri:level="1"><nlm:affiliation>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara</wicri:regionArea><wicri:noRegion>Guadalajara</wicri:noRegion></affiliation></author><author><name sortKey="Barbagelata, Alejandro" sort="Barbagelata, Alejandro" uniqKey="Barbagelata A" first="Alejandro" last="Barbagelata">Alejandro Barbagelata</name><affiliation wicri:level="2"><nlm:affiliation>Universidad Católica de Buenos Aires, Buenos Aires, Argentina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Universidad Católica de Buenos Aires, Buenos Aires, Argentina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Cristodulo Cortez, Roberto" sort="Cristodulo Cortez, Roberto" uniqKey="Cristodulo Cortez R" first="Roberto" last="Cristodulo-Cortez">Roberto Cristodulo-Cortez</name><affiliation><nlm:affiliation>Departamento de Medicina Interna, Hospital Obrero number 3 Caja Nacional de Salud, Santa Cruz de la Sierra, Bolivia.</nlm:affiliation><wicri:noCountry code="subField">Bolivia</wicri:noCountry></affiliation></author><author><name sortKey="Diaz Cucho, Omar A" sort="Diaz Cucho, Omar A" uniqKey="Diaz Cucho O" first="Omar A" last="Díaz-Cucho">Omar A. Díaz-Cucho</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao</wicri:regionArea><wicri:noRegion>Callao</wicri:noRegion></affiliation></author><author><name sortKey="Spaak, Jonas" sort="Spaak, Jonas" uniqKey="Spaak J" first="Jonas" last="Spaak">Jonas Spaak</name><affiliation wicri:level="3"><nlm:affiliation>Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Alfonso, Carlos E" sort="Alfonso, Carlos E" uniqKey="Alfonso C" first="Carlos E" last="Alfonso">Carlos E. Alfonso</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Valdivia Vega, Renzo" sort="Valdivia Vega, Renzo" uniqKey="Valdivia Vega R" first="Renzo" last="Valdivia-Vega">Renzo Valdivia-Vega</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Villavicencio Carranza, Mirko" sort="Villavicencio Carranza, Mirko" uniqKey="Villavicencio Carranza M" first="Mirko" last="Villavicencio-Carranza">Mirko Villavicencio-Carranza</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Ayala Garcia, Ricardo J" sort="Ayala Garcia, Ricardo J" uniqKey="Ayala Garcia R" first="Ricardo J" last="Ayala-García">Ricardo J. Ayala-García</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Castro Callirgos, Carlos A" sort="Castro Callirgos, Carlos A" uniqKey="Castro Callirgos C" first="Carlos A" last="Castro-Callirgos">Carlos A. Castro-Callirgos</name><affiliation wicri:level="1"><nlm:affiliation>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima</wicri:regionArea><wicri:noRegion>Lima</wicri:noRegion></affiliation></author><author><name sortKey="Gonzalez Hernandez, Luz A" sort="Gonzalez Hernandez, Luz A" uniqKey="Gonzalez Hernandez L" first="Luz A" last="González-Hernández">Luz A. González-Hernández</name><affiliation wicri:level="1"><nlm:affiliation>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.</nlm:affiliation><country xml:lang="fr">Mexique</country><wicri:regionArea>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara</wicri:regionArea><wicri:noRegion>Guadalajara</wicri:noRegion></affiliation></author><author><name sortKey="Bernales Salas, Eduardo F" sort="Bernales Salas, Eduardo F" uniqKey="Bernales Salas E" first="Eduardo F" last="Bernales-Salas">Eduardo F. Bernales-Salas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Coacalla Guerra, Johanna C" sort="Coacalla Guerra, Johanna C" uniqKey="Coacalla Guerra J" first="Johanna C" last="Coacalla-Guerra">Johanna C. Coacalla-Guerra</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Salinas Herrera, Cynthia D" sort="Salinas Herrera, Cynthia D" uniqKey="Salinas Herrera C" first="Cynthia D" last="Salinas-Herrera">Cynthia D. Salinas-Herrera</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa</wicri:regionArea><wicri:noRegion>Arequipa</wicri:noRegion></affiliation></author><author><name sortKey="Nicolosi, Liliana" sort="Nicolosi, Liliana" uniqKey="Nicolosi L" first="Liliana" last="Nicolosi">Liliana Nicolosi</name><affiliation wicri:level="1"><nlm:affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Basconcel, Mauro" sort="Basconcel, Mauro" uniqKey="Basconcel M" first="Mauro" last="Basconcel">Mauro Basconcel</name><affiliation wicri:level="1"><nlm:affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</nlm:affiliation><country xml:lang="fr">Argentine</country><wicri:regionArea>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires</wicri:regionArea><wicri:noRegion>Buenos Aires</wicri:noRegion></affiliation></author><author><name sortKey="Byrd, James B" sort="Byrd, James B" uniqKey="Byrd J" first="James B" last="Byrd">James B. Byrd</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Sharkoski, Tiffany" sort="Sharkoski, Tiffany" uniqKey="Sharkoski T" first="Tiffany" last="Sharkoski">Tiffany Sharkoski</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Bendezu Huasasquiche, Luis E" sort="Bendezu Huasasquiche, Luis E" uniqKey="Bendezu Huasasquiche L" first="Luis E" last="Bendezú-Huasasquiche">Luis E. Bendezú-Huasasquiche</name><affiliation wicri:level="1"><nlm:affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</nlm:affiliation><country xml:lang="fr">Pérou</country><wicri:regionArea>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao</wicri:regionArea><wicri:noRegion>Callao</wicri:noRegion></affiliation></author><author><name sortKey="Chittams, Jesse" sort="Chittams, Jesse" uniqKey="Chittams J" first="Jesse" last="Chittams">Jesse Chittams</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Edmonston, Daniel L" sort="Edmonston, Daniel L" uniqKey="Edmonston D" first="Daniel L" last="Edmonston">Daniel L. Edmonston</name><affiliation wicri:level="2"><nlm:affiliation>Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Vasquez, Charles R" sort="Vasquez, Charles R" uniqKey="Vasquez C" first="Charles R" last="Vasquez">Charles R. Vasquez</name><affiliation wicri:level="2"><nlm:affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Chirinos, Julio A" sort="Chirinos, Julio A" uniqKey="Chirinos J" first="Julio A" last="Chirinos">Julio A. Chirinos</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: julio.chirinos@uphs.upenn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author></analytic><series><title level="j">The Lancet. Respiratory medicine</title><idno type="eISSN">2213-2619</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.</p></div><div type="abstract" xml:lang="en"><p><b>FINDINGS</b></p><p>Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m</p></div><div type="abstract" xml:lang="en"><p><b>INTERPRETATION</b></p><p>Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>FUNDING</b></p><p>REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.</p></div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33422263</PMID><DateRevised><Year>2021</Year><Month>01</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2213-2619</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Jan</Month><Day>07</Day></PubDate></JournalIssue><Title>The Lancet. Respiratory medicine</Title><ISOAbbreviation>Lancet Respir Med</ISOAbbreviation></Journal><ArticleTitle>Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">S2213-2600(20)30558-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/S2213-2600(20)30558-0</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.</AbstractText><AbstractText Label="FINDINGS" NlmCategory="RESULTS">Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m<sup>2</sup> (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; β-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ<sup>2</sup> test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.</AbstractText><AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.</AbstractText><AbstractText Label="FUNDING" NlmCategory="BACKGROUND">REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.</AbstractText><CopyrightInformation>Copyright © 2021 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cohen</LastName><ForeName>Jordana B</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hanff</LastName><ForeName>Thomas C</ForeName><Initials>TC</Initials><AffiliationInfo><Affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author 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ValidYN="Y"><LastName>Rodriguez-Mori</LastName><ForeName>Juan E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Renna</LastName><ForeName>Nicolás</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Tara I</ForeName><Initials>TI</Initials><AffiliationInfo><Affiliation>Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Corrales-Medina</LastName><ForeName>Vicente</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, University of Ottawa and The 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Bolivia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Díaz-Cucho</LastName><ForeName>Omar A</ForeName><Initials>OA</Initials><AffiliationInfo><Affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spaak</LastName><ForeName>Jonas</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alfonso</LastName><ForeName>Carlos E</ForeName><Initials>CE</Initials><AffiliationInfo><Affiliation>Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Valdivia-Vega</LastName><ForeName>Renzo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Hospital Nacional 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A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernales-Salas</LastName><ForeName>Eduardo F</ForeName><Initials>EF</Initials><AffiliationInfo><Affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coacalla-Guerra</LastName><ForeName>Johanna C</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salinas-Herrera</LastName><ForeName>Cynthia D</ForeName><Initials>CD</Initials><AffiliationInfo><Affiliation>Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicolosi</LastName><ForeName>Liliana</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Basconcel</LastName><ForeName>Mauro</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Byrd</LastName><ForeName>James B</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sharkoski</LastName><ForeName>Tiffany</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bendezú-Huasasquiche</LastName><ForeName>Luis E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chittams</LastName><ForeName>Jesse</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Edmonston</LastName><ForeName>Daniel L</ForeName><Initials>DL</Initials><AffiliationInfo><Affiliation>Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vasquez</LastName><ForeName>Charles R</ForeName><Initials>CR</Initials><AffiliationInfo><Affiliation>Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chirinos</LastName><ForeName>Julio A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: julio.chirinos@uphs.upenn.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT04338009</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Lancet Respir Med</MedlineTA><NlmUniqueID>101605555</NlmUniqueID><ISSNLinking>2213-2600</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>10</Month><Day>18</Day></PubMedPubDate><PubMedPubDate 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