High Frequency Oscillatory Ventilation for Acute Respiratory Distress Syndrome (ARDS)

NCT01478802 | Terminated Phase 2 DMC

• 1 other identifier: 282-13475
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

Based on recent two-center results (Eur Respir J. 2011 Sep 1. \[Epub ahead of print\] PMID: 21885390) we hypothesized that intermittent High-frequency oscillation (HFO) combined with Recruitment Maneuvers (RMs) may beneficially affect the pathophysiology and survival of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS). Design: Randomized Controlled Trial. Intervention: Briefly, the HFO-RMs strategy of the intervention (HFO-RMs) group will comprise RMs (3/day) and an initial HFO session of 96 hours (HFO session can be interrupted before the 96-hour time point only if PaO2/FiO2 rises to \>200 mmHg for \>12 hours), followed by return to lung protective conventional mechanical ventilation (CMV) according to pre-specified oxygenation criteria. Within days 1-10 postrandomization, patients will be returned to HFO upon recurrence of their moderate-to-severe oxygenation disturbance. Patients of the control (CMV) group will receive lung protective CMV.

Conditions

Acute Respiratory Distress Syndrome

Keywords

Mechanical Ventilation; High frequency oscillation; Acute Respiratory Distress syndrome

Outcome Measures

Primary Outcomes (1)

• Survival to hospital discharge

  Patient discharged home while not requiring any form of ventilatory assistance.

  60-120 days

Secondary Outcomes (5)

• The number of ventilator-free days until day 60 post-randomization

  60 days

• The number of organ failure-free days until day 60 post-randomization

  60 days

• Complications

  60-120 days

• Physiological variables during the study intervention period

  10 days

• Inflammatory response

  5 days

Study Arms (2)

CMV Arm

ACTIVE COMPARATOR

Patients with moderate-to-severe Acute Respiratory Distress Syndrome treated solely with lung protective, low volume high positive end-expiratory pressure conventional mechanical ventilation (CMV) and recruitment maneuvers, as specified in detail in the Detailed Description section.

Device: Lung protective CMV

HFO-RMs Arm

EXPERIMENTAL

Patients with moderte-to-severe Acute Respiratory Distress Syndrome treated initially with a 96-hour-lasting session (session duration modifiable according to oxygenation criteria) of High-frequency oscillation (HFO)-Recruitment Maneuvers (RMs), and then with lung protective CMV interspersed to additional HFO-RMs sessions (if required according to study protocol). The protocolized use of HFO-RMs may extend until day 10 post-randomization, according to pre-specified oxygenation criteria. Full details are provided in the Detailed Description Section.

Device: HFO-RMs

Interventions

Lung protective CMV DEVICE

Low tidal volume-high positive end-expiratory pressure conventional mechanical ventilation (CMV) and recruitment maneuvers, as specified in detail in the Detailed Description Section.

CMV Arm

HFO-RMs DEVICE

Initial, 96-hour-lasting session (session duration modifiable according to oxygenation criteria) of High-frequency oscillation (HFO) combined with recruitment Maneuvers (RMs), followed by additional HFO-RMs sessions (if required according to the study protocol oxygenation criteria)during days 1-10. During the rest of the intervention period, patients will be treated with the same lung protective CMV strategy of the CMV arm. Additional details are provided in the Detailed Description Section.

HFO-RMs Arm

Eligibility Criteria

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

You may qualify if:

• early ARDS (establishment of the diagnosis within the preceding 72 hours) according to the criteria of the American-European Consensus Conference (5),
• Moderate-to-severe oxygenation disturbance \[defined as ratio of partial pressure of arterial oxygen (PaO2) to inspired oxygen fraction (FiO2)\<200 mmHg, while being ventilated with positive end-expiratory pressure (PEEP) set at ≥10 cmH2O for at least 12 hours,
• age 18-75 years, body weight \>40 Kg,

You may not qualify if:

• severe air leak (more than one chest tubes per hemithorax with persistent air leak for more than 72 hours),
• systolic blood pressure lower than 90 mmHg and/or mean blood pressure lower than 65 mmHg, despite maximum support with fluids and vasopressor drugs (i.e., norepinephrine infusion rate exceeding 0.5 μg/kg/min,
• significant heart disease (e.g. ejection fraction lower than 40%, history of pulmonary edema and active ischemic disease or myocardial infarction),
• severe chronic obstructive pulmonary disease (COPD) or asthma (e.g. previous admission for COPD/asthma, chronic treatment with corticosteroids for COPD/asthma, and chronic CO2 retention more than 50 mmHg),
• intracranial pathology with intracranial pressure \>20 mmHg, not responsive to maximum conservative treatment (e.g. hemorrhage, head injury, tumor, infection or acute ischemic stroke),
• chronic interstitial lung disease with bilateral lung infiltrates,
• lung biopsy or incision during the current admission,
• previous lung transplantation or bone marrow transplantation, i) pregnancy,
• immunosuppression, and
• participation in another clinical study.

Sponsors & Collaborators

• University of Athens: lead
• University of Thessaly: collaborator

Study Sites (2)

Evaggelismos General Hospital

Athens, Attica, GR-10675, Greece

Location

Larisa University General Hospital

Larissa, Thessaly, GR-41110, Greece

Location

Related Publications (21)

• Mentzelopoulos SD, Malachias S, Zintzaras E, Kokkoris S, Zakynthinos E, Makris D, Magira E, Markaki V, Roussos C, Zakynthinos SG. Intermittent recruitment with high-frequency oscillation/tracheal gas insufflation in acute respiratory distress syndrome. Eur Respir J. 2012 Mar;39(3):635-47. doi: 10.1183/09031936.00158810. Epub 2011 Sep 1.

  PMID: 21885390 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

• Mentzelopoulos SD, Theodoridou M, Malachias S, Sourlas S, Exarchos DN, Chondros D, Roussos C, Zakynthinos SG. Scanographic comparison of high frequency oscillation with versus without tracheal gas insufflation in acute respiratory distress syndrome. Intensive Care Med. 2011 Jun;37(6):990-9. doi: 10.1007/s00134-011-2162-z. Epub 2011 Mar 3.

  PMID: 21369813 BACKGROUND

• Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24. doi: 10.1164/ajrccm.149.3.7509706.

  PMID: 7509706 BACKGROUND

• Elsasser S, Schachinger H, Strobel W. Adjunctive drug treatment in severe hypoxic respiratory failure. Drugs. 1999 Sep;58(3):429-46. doi: 10.2165/00003495-199958030-00004.

  PMID: 10493271 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

• 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

• Ranieri VM, Brienza N, Santostasi S, Puntillo F, Mascia L, Vitale N, Giuliani R, Memeo V, Bruno F, Fiore T, Brienza A, Slutsky AS. Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension. Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1082-91. doi: 10.1164/ajrccm.156.4.97-01052.

  PMID: 9351606 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

• Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008 Feb 13;299(6):637-45. doi: 10.1001/jama.299.6.637.

  PMID: 18270352 BACKGROUND

• Grasso S, Mascia L, Del Turco M, Malacarne P, Giunta F, Brochard L, Slutsky AS, Marco Ranieri V. Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy. Anesthesiology. 2002 Apr;96(4):795-802. doi: 10.1097/00000542-200204000-00005.

  PMID: 11964585 BACKGROUND

• Derdak S. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adult patients. Crit Care Med. 2003 Apr;31(4 Suppl):S317-23. doi: 10.1097/01.CCM.0000057910.50618.EB.

  PMID: 12682459 BACKGROUND

• Mentzelopoulos SD, Roussos C, Zakynthinos SG. Prone position reduces lung stress and strain in severe acute respiratory distress syndrome. Eur Respir J. 2005 Mar;25(3):534-44. doi: 10.1183/09031936.05.00105804.

  PMID: 15738300 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

• 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

• Derdak S, Mehta S, Stewart TE, Smith T, Rogers M, Buchman TG, Carlin B, Lowson S, Granton J; Multicenter Oscillatory Ventilation For Acute Respiratory Distress Syndrome Trial (MOAT) Study Investigators. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med. 2002 Sep 15;166(6):801-8. doi: 10.1164/rccm.2108052.

  PMID: 12231488 BACKGROUND

• Ferguson ND, Chiche JD, Kacmarek RM, Hallett DC, Mehta S, Findlay GP, Granton JT, Slutsky AS, Stewart TE. Combining high-frequency oscillatory ventilation and recruitment maneuvers in adults with early acute respiratory distress syndrome: the Treatment with Oscillation and an Open Lung Strategy (TOOLS) Trial pilot study. Crit Care Med. 2005 Mar;33(3):479-86. doi: 10.1097/01.ccm.0000155785.23200.9e.

  PMID: 15753735 BACKGROUND

• Sud S, Sud M, Friedrich JO, Meade MO, Ferguson ND, Wunsch H, Adhikari NK. High frequency oscillation in patients with acute lung injury and acute respiratory distress syndrome (ARDS): systematic review and meta-analysis. BMJ. 2010 May 18;340:c2327. doi: 10.1136/bmj.c2327.

  PMID: 20483951 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Spyros D Mentzelopoulos, A. Professor

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

  PRINCIPAL INVESTIGATOR

• Spyros G Zakynthinos, Professor

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

  STUDY CHAIR

• Paschalis Sideras, PHD

  Institute of Biomedical Research of the Athens Academy of Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Intensive Care Medicine

Study Record Dates

• First Submitted: November 21, 2011
• First Posted: November 23, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 28, 2015

Record last verified: 2015-04

Locations

GR (2)