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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by Dr. Negrin University Hospital
Sponsor:
Collaborator:
Fundación Mutua Madrileña
Information provided by (Responsible Party):
Jesus Villar, Dr. Negrin University Hospital
ClinicalTrials.gov Identifier:
NCT01731795
First received: November 18, 2012
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Acute Respiratory Distress Syndrome
Drug: Dexamethasone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome

Resource links provided by NLM:


Further study details as provided by Dr. Negrin University Hospital:

Primary Outcome Measures:
  • Ventilator free-days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mortality [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    All-cause mortality at Day 60 after enrolment.


Other Outcome Measures:
  • organ failure [ Time Frame: ICU discharge ] [ Designated as safety issue: No ]
    Number of extrapulmonary organ system failures


Estimated Enrollment: 314
Study Start Date: December 2012
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No dexamethasone
Patients will be treated with conventional treatment
Active Comparator: Dexamethasone
Conventional treatment plus dexamethasone
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731795

Locations
Spain
Hospital Universitario Dr. Negrin Not yet recruiting
Las Palmas de Gran Canaria, Spain, 35010
Contact: Jesús Villar, MD, PhD    +34928449413    jesus.villar54@gmail.com   
Contact: Rosa L Fernández, MSc    +34928450082    rosalidia.fernandez@gmail.com   
Principal Investigator: Jesús Villar, MD, PhD         
Sponsors and Collaborators
Dr. Negrin University Hospital
Fundación Mutua Madrileña
Investigators
Principal Investigator: Jesús Villar, MD, PhD Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain
  More Information

No publications provided

Responsible Party: Jesus Villar, Director of Research, Dr. Negrin University Hospital
ClinicalTrials.gov Identifier: NCT01731795     History of Changes
Other Study ID Numbers: 2012-000775-17
Study First Received: November 18, 2012
Last Updated: November 21, 2012
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Dr. Negrin University Hospital:
acute respiratory distress syndrome, mechanical ventilation

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014