Dataset Information

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

ABSTRACT:

Importance

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients.

Objective

To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS.

Design, setting, and participants

Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients.

Interventions

Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n?=151) or standard care alone (n?=?148).

Main outcomes and measures

The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days.

Results

A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P?=?.04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events.

Conclusions and relevance

Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.

Trial registration

ClinicalTrials.gov Identifier: NCT04327401.

SUBMITTER: Tomazini BM

PROVIDER: S-EPMC7489411 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

Tomazini Bruno M BM Maia Israel S IS Cavalcanti Alexandre B AB Berwanger Otavio O Rosa Regis G RG Veiga Viviane C VC Avezum Alvaro A Lopes Renato D RD Bueno Flavia R FR Silva Maria Vitoria A O MVAO Baldassare Franca P FP Costa Eduardo L V ELV Moura Ricardo A B RAB Honorato Michele O MO Costa Andre N AN Damiani Lucas P LP Lisboa Thiago T Kawano-Dourado Letícia L Zampieri Fernando G FG Olivato Guilherme B GB Righy Cassia C Amendola Cristina P CP Roepke Roberta M L RML Freitas Daniela H M DHM Forte Daniel N DN Freitas Flávio G R FGR Fernandes Caio C F CCF Melro Livia M G LMG Junior Gedealvares F S GFS Morais Douglas Costa DC Zung Stevin S Machado Flávia R FR Azevedo Luciano C P LCP

JAMA 20201001 13

<h4>Importance</h4>Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients.<h4>Objective</h4>To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS.<h4>Design, setting, and participants</h4>Multicenter, randomized, open-label, clinical trial conduct ...[more]

PMID: 32876695

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Project description:ObjectivesThere is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors.DesignSecondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days.SettingLarge academic tertiary-care PICU.PatientsChildren with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation.InterventionsImplementation of a ventilator-weaning pathway on May 2016.Measurements and main resultsOf 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders.ConclusionsVentilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.

Project description:OBJECTIVES:To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome. DESIGN:Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis. SETTING:Two quaternary care PICUs. PATIENTS:Children with pediatric acute respiratory distress syndrome. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ? 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.

Project description:Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone is associated with increases in the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study. Setting: Intensive care unit. Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included. Interventions: None. Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) for the first 28 days. Defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray's proportional sub hazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg·kg-1 (IQR: 1-1.3 mg·kg-1) and median duration for 5 days (IQR: 5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61, 95% CI, 1.10-8.12, p = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95% CI: 0.02-0.45, p = 0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p = 0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR: 15-41 days] vs. 37 days [IQR: 23-52 days], p = 0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p = 0.052). However, 81% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

Dataset Information

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

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