title: Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial.
abstract: Although much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality.
  
  
  
  This is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment.
  
  
  
  This study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS.
  
  
  
  Registered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website ( NCT01731795 ).
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. jesus.villar54@gmail.com.|Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, 4th floor - South Wing, 35019, Las Palmas de Gran Canaria, Spain. jesus.villar54@gmail.com.|Keenan Research Center for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. jesus.villar54@gmail.com.
authors.forename: Jesús
authors.initials: J
authors.lastname: Villar
authors.affiliation: Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Belda
authors.affiliation: Intensive Care Unit, Hospital Virgen de La Luz, Cuenca, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Añón
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.|Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Blanco
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.|Division of Clinical Epidemiology and Biostatistics, Research Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Lina
authors.initials: L
authors.lastname: Pérez-Méndez
authors.affiliation: Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrando
authors.affiliation: Intensive Care Unit, Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Martínez
authors.affiliation: Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: Juan Alfonso
authors.initials: JA
authors.lastname: Soler
authors.affiliation: Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ambrós
authors.affiliation: Intensive Care Unit, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Muñoz
authors.affiliation: Intensive care Unit, Hospital Galdakao-Usansolo, Usansolo, Vizcaya, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Rivas
authors.affiliation: Intensive Care Unit, Hospital N.S. del Prado, Talavera de la Reina, Toledo, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Corpas
authors.affiliation: Intensive Care Unit, Hospital General de León, León, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Díaz-Dominguez
authors.affiliation: Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Soro
authors.affiliation: Biostatistics, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: García-Bello
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.|Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, 4th floor - South Wing, 35019, Las Palmas de Gran Canaria, Spain.
authors.forename: Rosa Lidia
authors.initials: RL
authors.lastname: Fernández
authors.affiliation: Department of Respiratory Care, Massachusetts General Hospital, Boston, MA, USA.|Department of Anesthesiology, Harvard University, Boston, MA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kacmarek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015982:Bias; D002985:Clinical Protocols; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone
keywords: Acute respiratory distress syndrome; Corticoids; Dexamethasone; Lung-protective ventilation; Positive end-expiratory pressure