Clinical and Biological Markers in Acute Respiratory Failure

NCT02019095 | Completed DMC

• 2 other identifiers: 309-27-11-201309ΣYN-12-1075
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 2

Brief Summary

In a recent experimental study, the investigators showed that the growth factor Activin A is expressed in the lungs of rats with the acute respiratory distress syndrome (ARDS) at levels that are comparable with those determined in the bronchoalveolar (BAL) lavage fluid from patients with ARDS. In the same study, the administration of the Activin A inhibitor Folistatin resulted in attenuation of the histological damage of the ARDS-afflicted rat lung. The precise role of Activin A/Folistatin in acute respiratory failure associated with acute lung inflammatory pathology has not been elucidated yet. Therefore, the purpose of the present, observational study is to investigate the role of Activin A/Folistatin in respiratory failure due to ARDS and/or ventilator-associated pneumonia (VAP), also in relation with other biochemical markers, such as cytokines and surfactant-related proteins.

Conditions

Ventilator-Associated Pneumonia; Acute Respiratory Distress Syndrome

Keywords

Pneumonia, Ventilator-Associated; Respiratory Distress Syndrome, Adult; Pulmonary Surfactant-Associated Proteins; activin A

Outcome Measures

Primary Outcomes (3)

• Change in Activin A, levels in BAL fluid from day 1 to day 5 post-enrollment

  Days 1-5 post-enrollment

• Change in cytokine levels in BAL fluid from day 1 to day 5 post-enrollment

  Days 1-5 post-enrollment

• Change in surfactant protein C levels in BAL fluid from day 1 to day 5 post-enrollment

  Days 1-5 post-enrollment

Secondary Outcomes (5)

• Survival to hospital discharge

  Days 1-60 (or until actual time point of hospital discharge) post-enrollment

• Organ Failure Free Days

  Days 1-60 post-enrollment

• Respiratory compliance and plateau airway pressure at 09:00 a.m. of days 1-10 post-enrollment

  Days 1-10 post-enrollment

• PaO2/FiO2, PaCO2, pHa, and central-venous oxygen saturation at 09:00 a.m. of days 1-10 post-enrollment.

  Days 1-10 post-enrollment

• Mean arterial and central-venous pressure, and norepinephrine infusion rate at 09:00 a.m. of days 1-10 post-enrollment

  Days 1-10 post-enrollment

Other Outcomes (1)

• Clinical course complications

  Days 1-60 post-enrollment (or until actual time point of hospital discharge)

Study Arms (1)

Acute Respiratory Failure - Bronchoalveolar lavage

Intensive care unit patients with acute respiratory failure due to ventilator-associated pneumonia or the acute respiratory distress syndrome. Bronchoalveolar lavage (BAL) fluid will be obtained on days 1 and 5 post-enrollment for the determination of biochemical markers, and microbiological studies.

Other: Bronchoscopy for the sampling of bronchoalveolar lavage (BAL) fluid

Interventions

Bronchoscopy for the sampling of bronchoalveolar lavage (BAL) fluid OTHER

Acute Respiratory Failure - Bronchoalveolar lavage

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Intensive care unit patients with acute respiratory failure due to ventilator-associated pneumonia or the acute respiratory distress syndrome.

You may qualify if:

• Ventilator-associated pneumonia and/or ARDS.
• PaO2 to fractional inspired oxygen (FiO2) of less than 400 mmHg.
• Age 18-75 years.
• Body weight of at least 40 Κg.

You may not qualify if:

• Significant air leak.
• Severe hemodynamic instability.
• Heart disease.
• Chronic obstructive pulmonary disease or asthma.
• Intracranial hypertension.
• Chronic interstitial lung disease.
• Lung biopsy or lobectomy/pneumonectomy during current admission.
• Prior lung or bone marrow transplantation.
• Pregnancy.
• Immunosuppression.
• Bleeding diathesis and/or coagulation disturbances.

Sponsors & Collaborators

• University of Athens: lead
• Academy of Athens: collaborator

Study Sites (2)

Evaggelismos General Hospital

Athens, Attica, GR-10675, Greece

Location

Academy of Athens, Biomedical Research Foundation, Center for Immunology and Transplantation, Athens, Greece

Athens, Attica, GR-11527, Greece

Location

Related Publications (21)

• Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1334-49. doi: 10.1056/NEJM200005043421806. No abstract available.

  PMID: 10793167 BACKGROUND

• Ware JH. The limitations of risk factors as prognostic tools. N Engl J Med. 2006 Dec 21;355(25):2615-7. doi: 10.1056/NEJMp068249. No abstract available.

  PMID: 17182986 BACKGROUND

• Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP; NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005 Jan;33(1):1-6; discussion 230-2. doi: 10.1097/01.ccm.0000149854.61192.dc.

  PMID: 15644641 BACKGROUND

• Ware LB, Eisner MD, Thompson BT, Parsons PE, Matthay MA. Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med. 2004 Oct 1;170(7):766-72. doi: 10.1164/rccm.200310-1434OC. Epub 2004 Jun 16.

  PMID: 15201135 BACKGROUND

• Eisner MD, Parsons P, Matthay MA, Ware L, Greene K; Acute Respiratory Distress Syndrome Network. Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax. 2003 Nov;58(11):983-8. doi: 10.1136/thorax.58.11.983.

  PMID: 14586055 BACKGROUND

• Calfee CS, Eisner MD, Parsons PE, Thompson BT, Conner ER Jr, Matthay MA, Ware LB; NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury. Intensive Care Med. 2009 Feb;35(2):248-57. doi: 10.1007/s00134-008-1235-0. Epub 2008 Aug 1.

  PMID: 18670758 BACKGROUND

• Parsons PE, Matthay MA, Ware LB, Eisner MD; National Heart, Lung, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L426-31. doi: 10.1152/ajplung.00302.2004. Epub 2004 Oct 29.

  PMID: 15516488 BACKGROUND

• Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med. 2007 Aug;35(8):1821-8. doi: 10.1097/01.CCM.0000221922.08878.49.

  PMID: 17667242 BACKGROUND

• Calfee CS, Ware LB, Eisner MD, Parsons PE, Thompson BT, Wickersham N, Matthay MA; NHLBI ARDS Network. Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury. Thorax. 2008 Dec;63(12):1083-9. doi: 10.1136/thx.2008.095588. Epub 2008 Jun 19.

  PMID: 18566109 BACKGROUND

• Ware LB. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med. 2006 Aug;27(4):337-49. doi: 10.1055/s-2006-948288.

  PMID: 16909368 BACKGROUND

• Apostolou E, Stavropoulos A, Sountoulidis A, Xirakia C, Giaglis S, Protopapadakis E, Ritis K, Mentzelopoulos S, Pasternack A, Foster M, Ritvos O, Tzelepis GE, Andreakos E, Sideras P. Activin-A overexpression in the murine lung causes pathology that simulates acute respiratory distress syndrome. Am J Respir Crit Care Med. 2012 Feb 15;185(4):382-91. doi: 10.1164/rccm.201105-0784OC. Epub 2011 Dec 8.

  PMID: 22161160 BACKGROUND

• Mentzelopoulos SD, Roussos C, Koutsoukou A, Sourlas S, Malachias S, Lachana A, Zakynthinos SG. Acute effects of combined high-frequency oscillation and tracheal gas insufflation in severe acute respiratory distress syndrome. Crit Care Med. 2007 Jun;35(6):1500-8. doi: 10.1097/01.CCM.0000265738.80832.BE.

  PMID: 17440419 BACKGROUND

• Mentzelopoulos SD, Malachias S, Kokkoris S, Roussos C, Zakynthinos SG. Comparison of high-frequency oscillation and tracheal gas insufflation versus standard high-frequency oscillation at two levels of tracheal pressure. Intensive Care Med. 2010 May;36(5):810-6. doi: 10.1007/s00134-010-1822-8. Epub 2010 Mar 16.

  PMID: 20232047 BACKGROUND

• Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.

  PMID: 20843245 BACKGROUND

• Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11.

  PMID: 19001507 BACKGROUND

• Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010 Mar 3;303(9):865-73. doi: 10.1001/jama.2010.218.

  PMID: 20197533 BACKGROUND

• Nakos G, Kitsiouli EI, Tsangaris I, Lekka ME. Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS. Alterations in leukocytes, proteins, PAF and surfactant components. Intensive Care Med. 1998 Apr;24(4):296-303. doi: 10.1007/s001340050571.

  PMID: 9609406 BACKGROUND

• Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F 2nd, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1896-903. doi: 10.1164/ajrccm.164.10.2104013.

  PMID: 11734443 BACKGROUND

• Clark JG, Milberg JA, Steinberg KP, Hudson LD. Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med. 1995 Jan 1;122(1):17-23. doi: 10.7326/0003-4819-122-1-199501010-00003.

  PMID: 7985891 BACKGROUND

• Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med. 1999 Dec;160(6):1843-50. doi: 10.1164/ajrccm.160.6.9901117.

  PMID: 10588595 BACKGROUND

• Madtes DK, Rubenfeld G, Klima LD, Milberg JA, Steinberg KP, Martin TR, Raghu G, Hudson LD, Clark JG. Elevated transforming growth factor-alpha levels in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1998 Aug;158(2):424-30. doi: 10.1164/ajrccm.158.2.9711112.

  PMID: 9700116 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bronchoalveolar Lavage Fluid

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Respiratory Distress Syndrome

Interventions

Bronchoscopy; Fluid Therapy

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Drug Therapy; Therapeutics

Study Officials

• Spyros D Mentzelopoulos, MD, PhD

  Evaggelismos General Hospital; Dept. Intensive Care Medicine, University of Athens Medical School

  PRINCIPAL INVESTIGATOR

• Spyros G Zakynthinos, MD, PhD

  Evaggelismos General Hospital; Dept. Intensive Care Medicine, University of Athens Medical School

  STUDY DIRECTOR

• Spyros G Zakynthinos, MD, PhD

  Evaggelismos General Hospital; Dept. Intensive Care Medicine, University of Athens Medical School

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Intensive Care Medicine

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: December 24, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 3, 2015

Record last verified: 2015-02

Locations

GR (2)