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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Effect of Intermittent High Frequency Oscillatory Ventilation on the Pathophysiology and Survival of Patients With the Acute Respiratory Distress Syndrome.

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.

Detailed Summary:

BACKGROUND AND RATIONALE Recent two-center results (1) support a beneficial effect of combined high-frequency oscillation (HFO), recruitment maneuvers (RMs) and tracheal gas insufflation (TGI) on the survival of patients with severe acute respiratory distress syndrome (ARDS). The addition of TGI to HFO improves gas-exchange (1-4); however, its value with respect to outcome still remains uncertain (1). TGI is likely useful in patients with very severe oxygenation disturbances and/or poor tolerance to hypercapnia (2).

The main goals of the present study are 1) The determination of the effect of the intermittent, combined use of HFO and RMs (HFO-RMs - intervention group) on the survival as compared to the best possible strategy of lung-protective conventional mechanical ventilation (CMV - control group); and 2) the elucidation of the mechanism of action of HFO on respiratory function and the ARDS-related inflammatory response.

The consecutive hypotheses supporting the conduct of the present trial can be summarized as follows:

The use of HFO + RMs will likely augment lung recruitment, with consequent improvements in oxygenation and lung compliance The HFO-related, physiological benefits will likely be maintained during the subsequent CMV, if an adequate positive end-expiratory pressure (PEEP) level is used (1).

Therefore, the following sequence of events is expected from the intermittent use of HFO-RMs:

• Lung Recruitment & Compliance →

  • Ventilation pressures during the subsequent CMV (as compared to pre-HFO CMV)&#
    Sponsor: University of Athens
    

    Current Primary Outcome: Survival to hospital discharge [ Time Frame: 60-120 days ]

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

    Original Primary Outcome: Same as current
    
    

    Current Secondary Outcome:

    • The number of ventilator-free days until day 60 post-randomization [ Time Frame: 60 days ]
      "60 minus days on ventilator until day 60 postrandomization"
    • The number of organ failure-free days until day 60 post-randomization [ Time Frame: 60 days ]
      "60 minus the days with an organ failure until day 60 postrandomization"
    • Complications [ Time Frame: 60-120 days ]
      Ventilation-related (e.g. barotrauma); Recruitment Maneuver-related (e.g. hypotension or desaturation); Tracheal Gas Insufflation-related (e.g. tracheal mucosal damage)
    • Physiological variables during the study intervention period [ Time Frame: 10 days ]
      Evolution of Physiological variables during the first 10 days post-randomization {comparison of gas-exchange, respiratory mechanics (14), hemodynamics, fluid balance of preceding 24 hours, and blood lactate; all between-group-compared variables to be concurrently determined within 8.30 to 9.00 a.m. of each one of the first 10 days post-randomization}
    • Inflammatory response [ Time Frame: 5 days ]
      Determination of markers of inflammation (cytokines and Activin A) in bronchoalveolar lavage fluid and peripheral blood at baseline and on day 5 post-randomization. Additional determination of surfactant activity on the same time points.
    
    
    

    Original Secondary Outcome: Same as current
    
    Information By: University of Athens
    

    Dates:
    Date Received: November 21, 2011
    Date Started: November 2011
    Date Completion:
    Last Updated: April 26, 2015
    Last Verified: April 2015