Ignite Creation Date:
2024-05-06 @ 3:11 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04545242
Status:
RECRUITING
Last Update Posted:
2024-02-20
First Post:
2020-09-05
Brief Title:
Efficacy of DEXamethasone in Patients With Acute Hypoxemic REspiratory Failure Caused by INfEctions
Sponsor:
Dr Negrin University Hospital
Organization:
Dr Negrin University Hospital
Study Overview
Official Title:
Efficacy of Higher vs Lower Doses of Dexamethasone in Patients With Acute Hypoxemic Respiratory Failure Including ARDS Caused by Infections Including COVID-19
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEXA-REFINE
Brief Summary:
Background There are no proven therapies specific for pulmonary dysfunction in patients with acute hypoxemic respiratory failure AHRF caused by infections including Covid-19 The full spectrum of AHRF ranges from mild respiratory tract illness to severe pneumonia acute respiratory distress syndrome ARDS multiorgan failure and death The efficacy of corticosteroids in AHRF and ARDS caused by infections remains controversial
Methods This is a multicenter randomized controlled open-label clinical trial testing dexamethasone in mechanically ventilated adult patients with established AHRF including ARDS caused by confirmed pulmonary or systemic infections admitted in a network of Spanish ICUs Eligible patients will be randomly assigned to receive dexamethasone either 6 mgd x 10 days or 20 mgd x 5 days followed by 10 mgd x 5 days The primary outcome is 60-day mortality The secondary outcome is the number of ventilator-free days at 28 days All analyses will be done according to the intention-to-treat principle
Methods This is a multicenter randomized controlled open-label clinical trial testing dexamethasone in mechanically ventilated adult patients with established AHRF including ARDS caused by confirmed pulmonary or systemic infections admitted in a network of Spanish ICUs Eligible patients will be randomly assigned to receive dexamethasone either 6 mgd x 10 days or 20 mgd x 5 days followed by 10 mgd x 5 days The primary outcome is 60-day mortality The secondary outcome is the number of ventilator-free days at 28 days All analyses will be done according to the intention-to-treat principle
Detailed Description:
Acute hypoxemic respiratory failure AHRF and its more severe form termed the acute respiratory distress syndrome ARDS is a catastrophic illness of multifactorial etiology characterized by a severe inflammatory process of the lung leading to hypoxemic respiratory failure requiring mechanical ventilation MV Pulmonary infections are the leading causes of AHRF and ARDS Translational research has established a strong association between dysregulated systemic and pulmonary inflammation and progression or delayed resolution of AHRF2 Glucocorticoid receptor-mediated downregulation of systemic and pulmonary inflammation is essential to accelerate disease resolution and restore tissue homeostasis and can be enhanced with glucocorticoid treatment
The COVID-19 pandemic is a critical moment for the world in which even industrially advanced countries have rapidly reached intensive care units ICUs saturation and intensivists are forced to make difficult ethical decisions that are uncommon outside war zones As with other bacterial or viral infections severe pneumonia is the main condition leading to AHRF and ARDS requiring weeks of MV with high mortality 35-55 in critically ill patients There has been great interest in the role of corticosteroids to attenuate the pulmonary and systemic damage in ARDS patients because of their potent anti-inflammatory and antifibrotic properties3 Corticosteroids have been off patent for greater than 20 years they are cheap and globally equitable However the efficacy of corticosteroids in AHRF including ARDS caused by infections remains controversial
Only two large randomized clinical trials RCT have shown that the administration of dexamethasone is able to reduce mortality in patients with AHRF Villar et al in Spain observed that moderate doses of dexamethasone 10-20 mgd x 10 days caused a 15 absolute reduction of 60-day mortality in patients with established moderate-to-severe ARDS from multiple etiologies Horby et al in the RECOVERY trial in Great Britain reported that dexamethasone at low doses 6 mgd x 10 days reduced 28-day mortality in patients with AHRF caused by COVID-19 These findings confirmed that corticosteroid therapy is associated with a sizable reduction in duration of MV and hospital mortality These two RCTs will change clinical practice for the management of AHRF and ARDS However there is a reasonable doubt whether dexamethasone at moderate doses 10-20 mgd would cause a greater reduction in mortality than 6 mgd Our goal in this study is to respond this question
The COVID-19 pandemic is a critical moment for the world in which even industrially advanced countries have rapidly reached intensive care units ICUs saturation and intensivists are forced to make difficult ethical decisions that are uncommon outside war zones As with other bacterial or viral infections severe pneumonia is the main condition leading to AHRF and ARDS requiring weeks of MV with high mortality 35-55 in critically ill patients There has been great interest in the role of corticosteroids to attenuate the pulmonary and systemic damage in ARDS patients because of their potent anti-inflammatory and antifibrotic properties3 Corticosteroids have been off patent for greater than 20 years they are cheap and globally equitable However the efficacy of corticosteroids in AHRF including ARDS caused by infections remains controversial
Only two large randomized clinical trials RCT have shown that the administration of dexamethasone is able to reduce mortality in patients with AHRF Villar et al in Spain observed that moderate doses of dexamethasone 10-20 mgd x 10 days caused a 15 absolute reduction of 60-day mortality in patients with established moderate-to-severe ARDS from multiple etiologies Horby et al in the RECOVERY trial in Great Britain reported that dexamethasone at low doses 6 mgd x 10 days reduced 28-day mortality in patients with AHRF caused by COVID-19 These findings confirmed that corticosteroid therapy is associated with a sizable reduction in duration of MV and hospital mortality These two RCTs will change clinical practice for the management of AHRF and ARDS However there is a reasonable doubt whether dexamethasone at moderate doses 10-20 mgd would cause a greater reduction in mortality than 6 mgd Our goal in this study is to respond this question
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None