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

This study has been terminated.
(Low rate of enrollment, in conjunction with inability of continuation of funding)
Sponsor:
Collaborator:
University of Thessaly
Information provided by (Responsible Party):
Spyros D. Mentzelopoulos, University of Athens
ClinicalTrials.gov Identifier:
NCT01478802
First received: November 21, 2011
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Acute Respiratory Distress Syndrome
Device: Lung protective CMV
Device: HFO-RMs
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Intermittent High Frequency Oscillatory Ventilation on the Pathophysiology and Survival of Patients With the Acute Respiratory Distress Syndrome.

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • Survival to hospital discharge [ Time Frame: 60-120 days ] [ Designated as safety issue: No ]
    Patient discharged home while not requiring any form of ventilatory assistance.


Secondary Outcome Measures:
  • The number of ventilator-free days until day 60 post-randomization [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    "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 ] [ Designated as safety issue: No ]
    "60 minus the days with an organ failure until day 60 postrandomization"

  • Complications [ Time Frame: 60-120 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 42
Study Start Date: November 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CMV Arm
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
Low tidal volume-high positive end-expiratory pressure conventional mechanical ventilation (CMV) and recruitment maneuvers, as specified in detail in the Detailed Description Section.
Experimental: HFO-RMs Arm
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
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. early ARDS (establishment of the diagnosis within the preceding 72 hours) according to the criteria of the American-European Consensus Conference (5),
  2. 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,
  3. age 18-75 years, body weight >40 Kg,

Exclusion Criteria:

  1. severe air leak (more than one chest tubes per hemithorax with persistent air leak for more than 72 hours),
  2. 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,
  3. significant heart disease (e.g. ejection fraction lower than 40%, history of pulmonary edema and active ischemic disease or myocardial infarction),
  4. 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),
  5. intracranial pathology with intracranial pressure >20 mmHg, not responsive to maximum conservative treatment (e.g. hemorrhage, head injury, tumor, infection or acute ischemic stroke),
  6. chronic interstitial lung disease with bilateral lung infiltrates,
  7. lung biopsy or incision during the current admission,
  8. previous lung transplantation or bone marrow transplantation, i) pregnancy,
  9. immunosuppression, and
  10. participation in another clinical study.
  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: NCT01478802

Locations
Greece
Evaggelismos General Hospital
Athens, Attica, Greece, GR-10675
Larisa University General Hospital
Larisa, Thessaly, Greece, GR-41110
Sponsors and Collaborators
University of Athens
University of Thessaly
Investigators
Principal Investigator: Spyros D Mentzelopoulos, A. Professor Evaggelismos Hospital, Dept. of Intensive Care Medicine, University of Athens Medical School
Study Chair: 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
  More Information

Publications:

Responsible Party: Spyros D. Mentzelopoulos, Assistant Professor in Intensive Care Medicine, University of Athens
ClinicalTrials.gov Identifier: NCT01478802     History of Changes
Other Study ID Numbers: 282-13475
Study First Received: November 21, 2011
Last Updated: December 12, 2013
Health Authority: Greece: Ministry of Health and Welfare

Keywords provided by University of Athens:
Mechanical Ventilation
High frequency oscillation
Acute Respiratory Distress syndrome

Additional relevant MeSH terms:
Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury

ClinicalTrials.gov processed this record on September 18, 2014