High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial
et al., Journal of Intensive Care Medicine, doi:10.1177/08850666211066799, NCT04395105, Dec 2021
RCT 98 mechanically ventilated patients with COVID-19-related ARDS showing no significant difference in ventilator-free days (VFD) at 28 days with high-dose dexamethasone (16mg/day for 5 days then 8mg/day for 5 days) versus low-dose dexamethasone (6mg/day for 10 days).
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risk of death, 10.0% lower, HR 0.90, p = 0.10, treatment 49, control 49, Cox proportional hazards, day 90.
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risk of death, no change, RR 1.00, p = 1.00, treatment 23 of 49 (46.9%), control 23 of 49 (46.9%), day 90.
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risk of death, 5.3% higher, RR 1.05, p = 1.00, treatment 20 of 49 (40.8%), control 19 of 49 (38.8%), day 28.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Maskin et al., 13 Dec 2021, Randomized Controlled Trial, Argentina, peer-reviewed, 13 authors, study period 17 June, 2020 - 27 March, 2021, trial NCT04395105 (history).
Contact: prodriguez@cemic.edu.ar.
Abstract: ## High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial
,
Luis Patricio Maskin, MD 1,2 , Ignacio Bonelli, MD 3 , Gabriel Leonardo Olarte, MD 4 , Fernando PalizasJr., MD 5 , Agostina E Velo, MD 1,3 , María Fernanda Lurbet, MD 1,3 , Pablo Lovazzano, PT 3 , Sophia Kotsias, MD 1 , Shiry Attie, MD 3 , Ignacio Lopez Saubidet, MD 3 Natalio D Baredes, MD 4 , Mariano Setten, PT 1 , and Pablo
Oscar Rodriguez, MD, PhD 1,2
Abstract
Objective: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19.
Design: Multicenter, randomized, open-label, clinical trial.
Participants: Consecutive patients with con fi rmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina
Intervention: 16 mg of dexamethasone intravenously daily for fi ve days followed by 8 mg of dexamethasone daily for fi ve days or 6 mg of dexamethasone intravenously daily for 10 days.
Main Outcome and Measures: The primary outcome was ventilator-free days during the fi rst 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the fi rst 28 days.
Results: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespeci fi ed secondary and safety outcomes showed a signi fi cant difference between treatment arms.
Conclusions: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose signi fi cantly improved the time required to liberate them from the ventilator
Keywords
acute respiratory distress syndrome, coronavirus, dexamethasone, randomized controlled trial, viral pneumonia
1 Intensive Care Unit, Hospital Universitario Sede Pombo (Instituto Universitario CEMIC, Centro de Educación Médica e Investigaciones Clínicas), Buenos Aires, Argentina
2 Pulmonary Section, CEMIC, Buenos Aires, Argentina
3 Intensive Care Unit, Hospital Universitario Sede Saavedra (Instituto Universitario CEMIC), Buenos Aires, Argentina
4 Intensive Care Unit, Sanatorio Sagrado Corazón, Buenos Aires, Argentina
5 Intensive Care Unit, Clínica Bazterrica, Buenos Aires, Argentina
Received September 16, 2021. Received revised November 10, 2021. Accepted November 29, 2021.
Corresponding Author:
Pablo O. Rodriguez, Unidad de T erapia Intensiva, Hospital Universitario Sede Pombo, CEMIC (Centro de Educación Médica e Investigaciones Clínicas), Av. Cnel. Diaz 2423, Zip Code: 1425, Ciudad Autónoma de Buenos Aires, Argentina.
Journal of Intensive Care Medicine 2022, Vol. 37(4) 491 -499 © The Author(s) 2021 Article reuse guidelines:..
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"abstract": "<jats:sec>\n <jats:title>Objective</jats:title>\n <jats:p>To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Design</jats:title>\n <jats:p>Multicenter, randomized, open-label, clinical trial.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Participants</jats:title>\n <jats:p>Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Intervention</jats:title>\n <jats:p>16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Main Outcome and Measures</jats:title>\n <jats:p>The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator</jats:p>\n </jats:sec>",
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Late treatment
is less effective
is less effective
