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Eur J Med Res
. 2024 Dec 23;29(1):616.
doi: 10.1186/s40001-024-02215-6. 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
Jan Maláska # 1 2 3 4 , Jan Stašek # 2 4 5 , Jan Máca 6 , Martin Kutěj 6 , František Duška 7 , Petr Kafka 8 , Olga Klementová 9 , Lenka Doubravská 9 , Jan Hruda 10 11 , Marek Fencl 10 11 , Tomáš Gabrhelík 12 , Libor Číž 12 , Jan Zatloukal 13 , Jiří Pouska 13 , Pavel Novotný 14 , Martin Balík 15 , Regina Demlová 16 , Jana Kubátová 16 , Jana Vinklerová 16 , Karolína Grodová 16 , Radka Štěpánová 16 , Adam Svobodník 16 , Milan Kratochvíl 1 , Jozef Klučka 1 , Petr Štourač 1 2 , Mervyn Singer 17 ; REMED Study Group
Collaborators, Affiliations
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/NCT...4663555&rank=1 and EudraCT: 2020-005887-70.
Keywords: ARDS; COVID-19; Dexamethasone; Long-term outcomes; Randomized clinical trial; Ventilator-free days.
. 2024 Dec 23;29(1):616.
doi: 10.1186/s40001-024-02215-6. 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
Jan Maláska # 1 2 3 4 , Jan Stašek # 2 4 5 , Jan Máca 6 , Martin Kutěj 6 , František Duška 7 , Petr Kafka 8 , Olga Klementová 9 , Lenka Doubravská 9 , Jan Hruda 10 11 , Marek Fencl 10 11 , Tomáš Gabrhelík 12 , Libor Číž 12 , Jan Zatloukal 13 , Jiří Pouska 13 , Pavel Novotný 14 , Martin Balík 15 , Regina Demlová 16 , Jana Kubátová 16 , Jana Vinklerová 16 , Karolína Grodová 16 , Radka Štěpánová 16 , Adam Svobodník 16 , Milan Kratochvíl 1 , Jozef Klučka 1 , Petr Štourač 1 2 , Mervyn Singer 17 ; REMED Study Group
Collaborators, Affiliations
- PMID: 39710693
- DOI: 10.1186/s40001-024-02215-6
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/NCT...4663555&rank=1 and EudraCT: 2020-005887-70.
Keywords: ARDS; COVID-19; Dexamethasone; Long-term outcomes; Randomized clinical trial; Ventilator-free days.