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Efficacy Study of Dexamethasone to Treat the Acute Respiratory Distress Syndrome (DEXA-ARDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01731795
Recruitment Status : Completed
First Posted : November 22, 2012
Last Update Posted : February 18, 2019
Fundación Mutua Madrileña
Asociación Científica Pulmón y Ventilación Mecánica
Information provided by (Responsible Party):
Jesus Villar, Dr. Negrin University Hospital

Tracking Information
First Submitted Date  ICMJE November 18, 2012
First Posted Date  ICMJE November 22, 2012
Last Update Posted Date February 18, 2019
Actual Study Start Date  ICMJE March 28, 2013
Actual Primary Completion Date February 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
Mortality [ Time Frame: 60 days ]
All-cause mortality at Day 60 after enrolment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 21, 2012)
organ failure [ Time Frame: ICU discharge ]
Number of extrapulmonary organ system failures
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Efficacy Study of Dexamethasone to Treat the Acute Respiratory Distress Syndrome
Official Title  ICMJE A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Respiratory Distress Syndrome
Intervention  ICMJE Drug: Dexamethasone
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)
Other Name: Dexamethasone Indukern
Study Arms  ICMJE
  • No Intervention: No dexamethasone
    Patients will be treated with conventional treatment
  • Active Comparator: Dexamethasone
    Conventional treatment plus dexamethasone
    Intervention: Drug: Dexamethasone
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 14, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2012)
Actual Study Completion Date  ICMJE February 12, 2019
Actual Primary Completion Date February 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01731795
Other Study ID Numbers  ICMJE 2012-000775-17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jesus Villar, Dr. Negrin University Hospital
Study Sponsor  ICMJE Dr. Negrin University Hospital
Collaborators  ICMJE
  • Fundación Mutua Madrileña
  • Asociación Científica Pulmón y Ventilación Mecánica
Investigators  ICMJE
Principal Investigator: Jesús Villar, MD, PhD Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain
PRS Account Dr. Negrin University Hospital
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP