Acute Respiratory Distress SyndromePhase 4DEXA-ARDSNCT01731795
Efficacy Study of Dexamethasone to Treat the Acute Respiratory Distress Syndrome
A Phase 4 study testing Dexamethasone in people with Acute Respiratory Distress Syndrome, run by Hospital Universitario de Gran Canaria Doctor Negrín at 2 sites in Spain.
Trial summary
BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids for the salvage of patients with severe acute lung injury in the early phase of their disease process, a situation that that has not… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 277 participants
- Where
- 2 sitesSpain
- Study dates
- 28 Mar 2013to 12 Feb 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥18 years old
- Patients must have acute onset of ARDS, as defined by the American-European Consensus Conference (AECC) criteria for ARDS: (i) having an initiating clinical condition (pneumonia, aspiration, inhalation injury, sepsis, trauma, acute pancreatitis, etc.; (ii) bilateral infiltrates on frontal chest radiograph; (iii) absence of left atrial hypertension, a pulmonary capillary wedge pressure (PCWP) less than 18 mm Hg, or no clinical signs of left heart failure; (iv) severe hypoxemia (a PaO2/FIO2 <200 mm Hg, regardless of FIO2 or positive end-expiratory pressure (PEEP)
- Be intubated and mechanically ventilated
- Have provided signed written informed consent from the patient or the patient's personal legal representative
Who cannot join
- Be a woman known to be pregnant or lactating
- Take part in another experimental treatment protocol (simultaneously)
- Brain death
- Terminal-stage cancer or other terminal disease
- Having do-not-resuscitate orders
- Being immune-compromised
Show all 10Show fewer
- Receiving corticosteroids or immunosuppressive drugs
- Patients in whom more than 24 hours had elapsed after initially meeting the AECC ARDS criteria before consent and results of initial standard ventilator settings could be obtained.
- Have severe chronic obstructive pulmonary disease (COPD)
- Have congestive heart failure
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital Universitario Dr. Negrin
Las Palmas de Gran Canaria, 35010
Hospital Clinico de Valencia
Valencia
About this study
Official title: A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome
BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids for the salvage of patients with severe acute lung injury in the early phase of their disease process, a situation that that has not been evaluated in most published trials. Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion.
HYPOTHESIS AND OBJECTIVES: The investigators hypothesize that adjunctive treatment with intravenous dexamethasone of patients with established ARDS might change the pulmonary and systemic inflammatory response and thereby will increase the number of ventilator-free days and will decrease the extremely high overall mortality. Our goal is to examine the effects of dexamethasone on length of duration of mechanical ventilation (assessed by number of ventilator-free days) and on mortality, in patients admitted into a network of Spanish intensive care units (ICUs) who still meet ARDS criteria at 24 hours after ARDS onset.
Read the detailed description
The acute respiratory distress syndrome (ARDS) is an inflammatory disease process of the lungs as a response to both direct and indirect insults, characterized clinically by severe hypoxemia, reduced lung compliance, and bilateral radiographic infiltrates. ARDS is caused by an insult to the alveolar-capillary membrane that results in increased permeability and subsequent interstitial and alveolar edema. The mechanisms by which a wide variety of insults can lead to this syndrome are not clear. It is useful to think of the pathogenesis of ARDS as a result of two different pathways: a direct insult on lung cells and an indirect insult as a result of an acute systemic inflammatory response.
Like any form of inflammation, acute lung injury during ARDS represents a complex process in which multiple cellular signalling pathways can propagate or inhibit lung injury. Death has traditionally been attributed to the underlying disease, the presence of sepsis and the failure of vital organ systems other than the lung. The association of ARDS with multiple system organ dysfunctions is not inevitable, but it certainly is common. It is postulated that local injury to the lungs (pneumonia, trauma, aspiration, gas inhalation) could set up a secondary diffuse inflammatory response resulting in damage to other organs.
Although much has evolved in our understanding of its pathogenesis and factors affecting patient outcome, still there is no specific pharmacologic treatment for ARDS. Despite advances in supportive measures and antibiotics, ARDS has a mortality rate of about 40-50% in most series and it is associated with significant health care costs. Patients with ARDS invariably require endotracheal intubation and mechanical ventilation (MV) to decrease the work of breathing and to improve oxygen transport. To date the only proven, widely accepted method of MV for ARDS is what is called "lung protective ventilation" using a low tidal volume strategy plus positive end-expiratory pressure (PEEP).
Corticoids seemed to be an ideal therapy for the acute lung injury in ARDS, given their potent anti-inflammatory and antifibrotic properties. They switch off genes that encode pro-inflammatory cytokines and switch on genes that encode anti-inflammatory cytokines. It has been reported that low doses of corticosteroids prevent an extended cytokine response and might accelerate the resolution of pulmonary and systemic inflammation in pneumonia.
Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion. However, dexametasone has potent anti-inflammatory effects and weak mineralocorticoid effects compared with other corticosteroids. Dexamethasone has a long-lasting effect, allowing for a once-a-day regimen. Whether addition of dexamethasone to conventional supportive treatment benefits ARDS patients is unknown, it has been used in patients with sepsis, septic shock, pneumonia, trauma, and meningitis, all of them causes of ARDS.
The investigators justify the need of our study based on the positive results of two recent clinical trials: (i) Meijvis et al (Lancet 2011) showed that dexamethasone (5 mg/day) for 4 days was able to reduce length of hospital stay in 304 patients with bacterial pneumonia when added to the conventional treatment; (ii) Azoulay et al (Eur Respir J 2011) showed that dexamethasone (10 mg/6h), when added to chemotherapy and conventional ICU management, caused less respiratory deterioration and lower ICU mortality in 40 patients with acute lung injury resulting from leukaemia.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Dexamethasone
- Keywords
- acute respiratory distress syndrome, mechanical ventilation
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Dexamethasone Indukern
Dexamethasone (20 mg/iv/daily/from Day 1 of randomization during 5 days, followed by 10 mg/iv/daily/ from Day 6 to 10 of randomization)
| Study group | Role | What they receive |
|---|---|---|
| No dexamethasone | No intervention | Patients will be treated with conventional treatment |
| Dexamethasone | Active comparator | Conventional treatment plus dexamethasone Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilator free-days
Number of ventilator free-days (VFDs) at Day 28 (defined as days alive and free from mechanical ventilation at day 28 after intubation. For subjects ventilated ≥28 days and for subjects who die, VFD is 0.
Measured: 28 days
Secondary outcomes (1)
Mortality
All-cause mortality at Day 60 after enrolment.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2012 (estimated)
- Study start28 Mar 2013
- Primary completion12 Feb 2019
- Study completion12 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 277 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario de Gran Canaria Doctor Negrín
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Mutua Madrileña, Asociación Científica Pulmón y Ventilación Mecánica
- Responsible party
- Principal investigator, Jesus Villar, Hospital Universitario de Gran Canaria Doctor Negrín
- Investigators
- Jesús Villar, MD, PhD, Principal investigator, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01731795
- Sponsor's protocol ID
- 2012-000775-17
- Acronym
- DEXA-ARDS
- Status last verified
- Feb 2019
- First submitted
- 18 Nov 2012
- Last updated
- 18 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7.
PubMed 32043986Sweeney RM, McAuley DF. Prolonged glucocorticoid treatment in acute respiratory distress syndrome - Authors' reply. Lancet. 2017 Apr 15;389(10078):1516-1517. doi: 10.1016/S0140-6736(17)30953-4. No abstract available.
PubMed 28422025Villar J, Belda J, Anon JM, Blanco J, Perez-Mendez L, Ferrando C, Martinez D, Soler JA, Ambros A, Munoz T, Rivas R, Corpas R, Diaz-Dominguez FJ, Soro M, Garcia-Bello MA, Fernandez RL, Kacmarek RM; DEXA-ARDS Network. Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial. Trials. 2016 Jul 22;17:342. doi: 10.1186/s13063-016-1456-4.
PubMed 27449641
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT01731795
- Acronym / sponsor ID
- DEXA-ARDS / 2012-000775-17
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- acute respiratory distress syndrome, mechanical ventilation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- Hospital Universitario de Gran Canaria Doctor NegrínUniversity, hospital or other
- Collaborators
- Fundación Mutua Madrileña, Asociación Científica Pulmón y Ventilación Mecánica
- Study start
- 28 Mar 2013 (actual)
- Primary completion
- 12 Feb 2019 (actual)
- Study completion
- 12 Feb 2019 (actual)
- First posted
- 22 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids for the salvage of patients with severe acute lung injury in the early phase of their disease process, a situation that that has not been evaluated in most published trials. Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion.
HYPOTHESIS AND OBJECTIVES: The investigators hypothesize that adjunctive treatment with intravenous dexamethasone of patients with established ARDS might change the pulmonary and systemic inflammatory response and thereby will increase the number of ventilator-free days and will decrease the extremely high overall mortality. Our goal is to examine the effects of dexamethasone on length of duration of mechanical ventilation (assessed by number of ventilator-free days) and on mortality, in patients admitted into a network of Spanish intensive care units (ICUs) who still meet ARDS criteria at 24 hours after ARDS onset.
Detailed description
The acute respiratory distress syndrome (ARDS) is an inflammatory disease process of the lungs as a response to both direct and indirect insults, characterized clinically by severe hypoxemia, reduced lung compliance, and bilateral radiographic infiltrates. ARDS is caused by an insult to the alveolar-capillary membrane that results in increased permeability and subsequent interstitial and alveolar edema. The mechanisms by which a wide variety of insults can lead to this syndrome are not clear. It is useful to think of the pathogenesis of ARDS as a result of two different pathways: a direct insult on lung cells and an indirect insult as a result of an acute systemic inflammatory response.
Like any form of inflammation, acute lung injury during ARDS represents a complex process in which multiple cellular signalling pathways can propagate or inhibit lung injury. Death has traditionally been attributed to the underlying disease, the presence of sepsis and the failure of vital organ systems other than the lung. The association of ARDS with multiple system organ dysfunctions is not inevitable, but it certainly is common. It is postulated that local injury to the lungs (pneumonia, trauma, aspiration, gas inhalation) could set up a secondary diffuse inflammatory response resulting in damage to other organs.
Although much has evolved in our understanding of its pathogenesis and factors affecting patient outcome, still there is no specific pharmacologic treatment for ARDS. Despite advances in supportive measures and antibiotics, ARDS has a mortality rate of about 40-50% in most series and it is associated with significant health care costs. Patients with ARDS invariably require endotracheal intubation and mechanical ventilation (MV) to decrease the work of breathing and to improve oxygen transport. To date the only proven, widely accepted method of MV for ARDS is what is called "lung protective ventilation" using a low tidal volume strategy plus positive end-expiratory pressure (PEEP).
Corticoids seemed to be an ideal therapy for the acute lung injury in ARDS, given their potent anti-inflammatory and antifibrotic properties. They switch off genes that encode pro-inflammatory cytokines and switch on genes that encode anti-inflammatory cytokines. It has been reported that low doses of corticosteroids prevent an extended cytokine response and might accelerate the resolution of pulmonary and systemic inflammation in pneumonia.
Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion. However, dexametasone has potent anti-inflammatory effects and weak mineralocorticoid effects compared with other corticosteroids. Dexamethasone has a long-lasting effect, allowing for a once-a-day regimen. Whether addition of dexamethasone to conventional supportive treatment benefits ARDS patients is unknown, it has been used in patients with sepsis, septic shock, pneumonia, trauma, and meningitis, all of them causes of ARDS.
The investigators justify the need of our study based on the positive results of two recent clinical trials: (i) Meijvis et al (Lancet 2011) showed that dexamethasone (5 mg/day) for 4 days was able to reduce length of hospital stay in 304 patients with bacterial pneumonia when added to the conventional treatment; (ii) Azoulay et al (Eur Respir J 2011) showed that dexamethasone (10 mg/6h), when added to chemotherapy and conventional ICU management, caused less respiratory deterioration and lower ICU mortality in 40 patients with acute lung injury resulting from leukaemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No dexamethasone | No intervention | –Patients will be treated with conventional treatment |
| Dexamethasone | Active comparator | Drug: DexamethasoneConventional treatment plus dexamethasone |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years old
- Patients must have acute onset of ARDS, as defined by the American-European Consensus Conference (AECC) criteria for ARDS: (i) having an initiating clinical condition (pneumonia, aspiration, inhalation injury, sepsis, trauma, acute pancreatitis, etc.; (ii) bilateral infiltrates on frontal chest radiograph; (iii) absence of left atrial hypertension, a pulmonary capillary wedge pressure (PCWP) less than 18 mm Hg, or no clinical signs of left heart failure; (iv) severe hypoxemia (a PaO2/FIO2 <200 mm Hg, regardless of FIO2 or positive end-expiratory pressure (PEEP)
- Be intubated and mechanically ventilated
- Have provided signed written informed consent from the patient or the patient's personal legal representative
Key exclusion criteria (10 listed)
- Be a woman known to be pregnant or lactating
- Take part in another experimental treatment protocol (simultaneously)
- Brain death
- Terminal-stage cancer or other terminal disease
- Having do-not-resuscitate orders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: Dexamethasone IndukernDexamethasone (20 mg/iv/daily/from Day 1 of randomization during 5 days, followed by 10 mg/iv/daily/ from Day 6 to 10 of randomization) | Drug | Dexamethasone |
Primary outcome
Ventilator free-days
Time frame: 28 days
Number of ventilator free-days (VFDs) at Day 28 (defined as days alive and free from mechanical ventilation at day 28 after intubation. For subjects ventilated ≥28 days and for subjects who die, VFD is 0.
1 secondary outcome
Mortality
Time frame: 60 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2019.
- Derived from this study: PubMed 32043986Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7.
- Derived from this study: PubMed 28422025Sweeney RM, McAuley DF. Prolonged glucocorticoid treatment in acute respiratory distress syndrome - Authors' reply. Lancet. 2017 Apr 15;389(10078):1516-1517. doi: 10.1016/S0140-6736(17)30953-4. No abstract available.
- Derived from this study: PubMed 27449641Villar J, Belda J, Anon JM, Blanco J, Perez-Mendez L, Ferrando C, Martinez D, Soler JA, Ambros A, Munoz T, Rivas R, Corpas R, Diaz-Dominguez FJ, Soro M, Garcia-Bello MA, Fernandez RL, Kacmarek RM; DEXA-ARDS Network. Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial. Trials. 2016 Jul 22;17:342. doi: 10.1186/s13063-016-1456-4.
- Individual participant dataSharing planned: No
Related trials for Acute Respiratory Distress Syndrome
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesús Villar, MD, PhD principal investigator
Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexamethasone in people with Acute Respiratory Distress Syndrome, run by Hospital Universitario de Gran Canaria Doctor Negrín at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator free-days (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01731795, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2019.