Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial
Abstract Background Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 m...
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2024-12-01
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| Online Access: | https://doi.org/10.1186/s40001-024-02215-6 |
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| author | Jan Maláska Jan Stašek Jan Máca Martin Kutěj František Duška Petr Kafka Olga Klementová Lenka Doubravská Jan Hruda Marek Fencl Tomáš Gabrhelík Libor Číž Jan Zatloukal Jiří Pouska Pavel Novotný Martin Balík Regina Demlová Jana Kubátová Jana Vinklerová Karolína Grodová Radka Štěpánová Adam Svobodník Milan Kratochvíl Jozef Klučka Petr Štourač Mervyn Singer the REMED Study Group |
| author_facet | Jan Maláska Jan Stašek Jan Máca Martin Kutěj František Duška Petr Kafka Olga Klementová Lenka Doubravská Jan Hruda Marek Fencl Tomáš Gabrhelík Libor Číž Jan Zatloukal Jiří Pouska Pavel Novotný Martin Balík Regina Demlová Jana Kubátová Jana Vinklerová Karolína Grodová Radka Štěpánová Adam Svobodník Milan Kratochvíl Jozef Klučka Petr Štourač Mervyn Singer the REMED Study Group |
| author_sort | Jan Maláska |
| collection | DOAJ |
| description | Abstract Background Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. Methods In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1–5, 10 mg/day on days 6–10) or standard-dose dexamethasone (6 mg/d, days 1–10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. Results The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5–66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI − 2.12–3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. Conclusions Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020–005887-70. |
| format | Article |
| id | doaj-art-43c8baacdf924df6b0777ee0fbcf0065 |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-43c8baacdf924df6b0777ee0fbcf00652025-08-20T02:43:35ZengBMCEuropean Journal of Medical Research2047-783X2024-12-0129111110.1186/s40001-024-02215-6Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trialJan Maláska0Jan Stašek1Jan Máca2Martin Kutěj3František Duška4Petr Kafka5Olga Klementová6Lenka Doubravská7Jan Hruda8Marek Fencl9Tomáš Gabrhelík10Libor Číž11Jan Zatloukal12Jiří Pouska13Pavel Novotný14Martin Balík15Regina Demlová16Jana Kubátová17Jana Vinklerová18Karolína Grodová19Radka Štěpánová20Adam Svobodník21Milan Kratochvíl22Jozef Klučka23Petr Štourač24Mervyn Singer25the REMED Study GroupDepartment of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk UniversityDepartment of Simulation Medicine, Faculty of Medicine, Masaryk UniversityDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University OstravaDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava and Faculty of Medicine, University OstravaDepartment of Anaesthesia and Intensive Care, University Hospital Královské Vinohrady and the Third Faculty of Medicine, Charles UniversityDepartment of Anaesthesia and Intensive Care, University Hospital Královské Vinohrady and the Third Faculty of Medicine, Charles UniversityDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Olomouc and Faculty of Medicine, Palacky UniversityDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Olomouc and Faculty of Medicine, Palacky UniversityDepartment of Anaesthesiology and Intensive Care Medicine, St. Anne’s University Hospital and Faculty of Medicine, Masaryk UniversityDepartment of Anaesthesiology and Intensive Care Medicine, St. Anne’s University Hospital and Faculty of Medicine, Masaryk UniversityDepartment of Anaesthesiology and Intensive Care Medicine, Tomáš Baťa Regional HospitalDepartment of Anaesthesiology and Intensive Care Medicine, Tomáš Baťa Regional HospitalDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Pilsen and Faculty of Medicine in Pilsen, Charles UniversityDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Pilsen and Faculty of Medicine in Pilsen, Charles UniversityDepartment of Anaesthesiology and Intensive Care, Military University Hospital Praha and the First Faculty of Medicine Charles UniversityDepartment of Anaesthesia and Intensive Care, General University Hospital in Prague and the First Faculty of Medicine, Charles UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk UniversityDepartment of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk UniversityDepartment of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk UniversityDepartment of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk UniversityBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College LondonAbstract Background Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. Methods In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1–5, 10 mg/day on days 6–10) or standard-dose dexamethasone (6 mg/d, days 1–10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. Results The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5–66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI − 2.12–3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. Conclusions Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020–005887-70.https://doi.org/10.1186/s40001-024-02215-6COVID-19ARDSDexamethasoneRandomized clinical trialVentilator-free daysLong-term outcomes |
| spellingShingle | Jan Maláska Jan Stašek Jan Máca Martin Kutěj František Duška Petr Kafka Olga Klementová Lenka Doubravská Jan Hruda Marek Fencl Tomáš Gabrhelík Libor Číž Jan Zatloukal Jiří Pouska Pavel Novotný Martin Balík Regina Demlová Jana Kubátová Jana Vinklerová Karolína Grodová Radka Štěpánová Adam Svobodník Milan Kratochvíl Jozef Klučka Petr Štourač Mervyn Singer the REMED Study Group Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial European Journal of Medical Research COVID-19 ARDS Dexamethasone Randomized clinical trial Ventilator-free days Long-term outcomes |
| title | Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial |
| title_full | Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial |
| title_fullStr | Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial |
| title_full_unstemmed | Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial |
| title_short | Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial |
| title_sort | effects of two different dexamethasone dosing regimens on ventilator free days and long term mortality in covid 19 patients with moderate to severe ards the remed randomized clinical trial |
| topic | COVID-19 ARDS Dexamethasone Randomized clinical trial Ventilator-free days Long-term outcomes |
| url | https://doi.org/10.1186/s40001-024-02215-6 |
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