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Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)

BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high...

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Autores principales: Daenen, Katrijn, Huijben, Jilske A, Boyd, Anders, Bos, Lieuwe D J, Stoof, Sara C M, van Willigen, Hugo, Gommers, Diederik A M P J, Moeniralam, Hazra S, den Uil, Corstiaan A, Juffermans, Nicole P, Kant, Merijn, Valkenburg, Abraham J, Pillay, Janesh, van Meenen, David M P, Paulus, Frederique, Schultz, Marcus J, Dalm, Virgil A S H, van Gorp, Eric C M, Schinkel, Janke, Endeman, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JMIR Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276318/
https://www.ncbi.nlm.nih.gov/pubmed/37266993
http://dx.doi.org/10.2196/48183
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author Daenen, Katrijn
Huijben, Jilske A
Boyd, Anders
Bos, Lieuwe D J
Stoof, Sara C M
van Willigen, Hugo
Gommers, Diederik A M P J
Moeniralam, Hazra S
den Uil, Corstiaan A
Juffermans, Nicole P
Kant, Merijn
Valkenburg, Abraham J
Pillay, Janesh
van Meenen, David M P
Paulus, Frederique
Schultz, Marcus J
Dalm, Virgil A S H
van Gorp, Eric C M
Schinkel, Janke
Endeman, Henrik
author_facet Daenen, Katrijn
Huijben, Jilske A
Boyd, Anders
Bos, Lieuwe D J
Stoof, Sara C M
van Willigen, Hugo
Gommers, Diederik A M P J
Moeniralam, Hazra S
den Uil, Corstiaan A
Juffermans, Nicole P
Kant, Merijn
Valkenburg, Abraham J
Pillay, Janesh
van Meenen, David M P
Paulus, Frederique
Schultz, Marcus J
Dalm, Virgil A S H
van Gorp, Eric C M
Schinkel, Janke
Endeman, Henrik
author_sort Daenen, Katrijn
collection PubMed
description BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183
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spelling pubmed-102763182023-06-18 Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT) Daenen, Katrijn Huijben, Jilske A Boyd, Anders Bos, Lieuwe D J Stoof, Sara C M van Willigen, Hugo Gommers, Diederik A M P J Moeniralam, Hazra S den Uil, Corstiaan A Juffermans, Nicole P Kant, Merijn Valkenburg, Abraham J Pillay, Janesh van Meenen, David M P Paulus, Frederique Schultz, Marcus J Dalm, Virgil A S H van Gorp, Eric C M Schinkel, Janke Endeman, Henrik JMIR Res Protoc Protocol BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183 JMIR Publications 2023-06-02 /pmc/articles/PMC10276318/ /pubmed/37266993 http://dx.doi.org/10.2196/48183 Text en ©Katrijn Daenen, Jilske A Huijben, Anders Boyd, Lieuwe D J Bos, Sara C M Stoof, Hugo van Willigen, Diederik A M P J Gommers, Hazra S Moeniralam, Corstiaan A den Uil, Nicole P Juffermans, Merijn Kant, Abraham J Valkenburg, Janesh Pillay, David M P van Meenen, Frederique Paulus, Marcus J Schultz, Virgil A S H Dalm, Eric C M van Gorp, Janke Schinkel, Henrik Endeman, PRoVENT- and PRoAcT-COVID Collaborative Group. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.06.2023. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.
spellingShingle Protocol
Daenen, Katrijn
Huijben, Jilske A
Boyd, Anders
Bos, Lieuwe D J
Stoof, Sara C M
van Willigen, Hugo
Gommers, Diederik A M P J
Moeniralam, Hazra S
den Uil, Corstiaan A
Juffermans, Nicole P
Kant, Merijn
Valkenburg, Abraham J
Pillay, Janesh
van Meenen, David M P
Paulus, Frederique
Schultz, Marcus J
Dalm, Virgil A S H
van Gorp, Eric C M
Schinkel, Janke
Endeman, Henrik
Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title_full Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title_fullStr Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title_full_unstemmed Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title_short Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT)
title_sort optimal dosing and timing of high-dose corticosteroid therapy in hospitalized patients with covid-19: study protocol for a retrospective observational multicenter study (select)
topic Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276318/
https://www.ncbi.nlm.nih.gov/pubmed/37266993
http://dx.doi.org/10.2196/48183
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