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Study of a Novel Technique of Mechanical Ventilation in Patients With Severe Acute Respiratory Failure (HFO-TGI-2)

This study has been completed.
Sponsor:
Collaborator:
University of Thessaly
Information provided by (Responsible Party):
Spyros D. Mentzelopoulos, University of Athens
ClinicalTrials.gov Identifier:
NCT00637507
First received: March 4, 2008
Last updated: June 21, 2014
Last verified: June 2014
  Purpose

The investigators have recently demonstrated the beneficial effects of combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) on the respiratory physiology [1,2] of patients with severe acute respiratory distress syndrome (ARDS) (NCT00416260). Preliminary short-term survival results were also encouraging. Consequently, in the present clinical trial, the investigators intend to increase the size of the studied population, in order to evaluate the effect of HFO-TGI on survival with adequate statistical power. Furthermore, the investigators intend to elucidate the mechanism of the HFO-TGI-related physiological benefit.


Condition Intervention Phase
Respiratory Distress Syndrome
Other: High-frequency Oscillation and Tracheal Gas Insufflation
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: Phase II/Phase III Study of the Effect of Combined High-frequency Oscillation and Tracheal Gas Insufflation on the Survival to Hospital Discharge of Patients With Severe Acute Respiratory Distress Syndrome

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • Survival to days 28 and 60 post-randomization, and to Hospital Discharge [ Time Frame: 28 days to more than 60 days post-randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Lung recruitment during the study-intervention period [ Time Frame: 8 days post-randomization ] [ Designated as safety issue: No ]
  • Evolution of Gas-exchange, Hemodynamics, and Respiratory Mechanics during the Study Intervention Period [ Time Frame: 8-10 days post-randomization ] [ Designated as safety issue: No ]
  • Ventilator Free Days [ Time Frame: 60 days post-randomization ] [ Designated as safety issue: No ]
  • Organ or System Failure Free Days [ Time Frame: 60 days post-randomization ] [ Designated as safety issue: No ]
  • Occurrence of barotrauma (i.e., any new pneumothorax, pneumomediastinum, or subcutaneous emphysema, or pneumatocele > 2 cm) [ Time Frame: 60 days post-randomization ] [ Designated as safety issue: Yes ]
  • Occurence of Tracheal Mucosal Injury due to use of Tracheal Gas Insufflation [ Time Frame: 8-10 days post-randomization ] [ Designated as safety issue: Yes ]

Enrollment: 124
Study Start Date: March 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 2
Patients treated solely with a pressure- and volume-limited ventilatory strategy (target plateau pressure of 30 cm H2O) aimed at minimizing lung stress and strain, and thus, ventilator-induced lung injury.
Experimental: 1
Intermittent application of High-frequency Oscillation (HFO) and Tracheal Gas Insufflation (TGI) according to pre-specified criteria described in the Detailed Description. HFO-TGI sessions are interspersed with lung protective conventional mechanical ventilation until the PaO2/FiO2 ratio stabilizes at >150 mm Hg.
Other: High-frequency Oscillation and Tracheal Gas Insufflation
Patients will receive daily sessions of High-frequency Oscillation and Tracheal Gas Insufflation (HFO-TGI), which will last at least 6 hours. These sessions will comprise a recruitment period of at least 90 min, a stabilization period of at least 4 hours, and a weaning period of at least 60 min. The HFO-TGI strategy will be aimed at initially maximizing PaO2/FiO2 without causing hemodynamic compromise (e.g., >10% reduction in cardiac output/index), and subsequently maintaining PaO2/FiO2 >150 mm Hg, while gradually reducing mPaw to 4-6 cm H2O below its initial setting. The weaning from TGI and HFO will be according to the reversal of the oxygenation criterion that mandated their use (see also Detailed Description).
Other Name: HFO-TGI

  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:

  • Age 18-75 years
  • Body weight > 40 kg
  • Endotracheal intubation and mechanical ventilation
  • Diagnosis of ARDS established within preceding 72 h
  • Severe oxygenation disturbances: PaO2/FiO2 <150 mm Hg sustained for 12 h, despite being ventilated with PEEP ≥8 cm H2O

Exclusion Criteria:

  • Active air leak or recent severe air leak (severe air leak: > 1 chest tube per hemithorax with persistent gas leak for > 72 h)
  • Severe hemodynamic instability (i.e., systolic arterial pressure < 90 mm Hg despite volume loading and norepinephrine infusion at ≥ 0.5 μg/kg/min)
  • Significant heart disease (i.e., ejection fraction <40 %, and/or history of pulmonary edema, and/or active coronary ischemia or myocardial infarction)
  • Significant chronic obstructive pulmonary disease (COPD) or asthma {i.e., previous admissions for COPD/asthma, chronic corticosteroid therapy for COPD/asthma, and documented chronic CO2 retention leading to a baseline PaCO2 of > 50 mm Hg (for COPD)}
  • Uncontrollable intracranial hypertension (i.e., intracranial pressure >20 mm Hg despite deep sedation, analgesia, hyperosmolar therapy, and minute ventilation titrated to PaCO2 = 35 mm Hg)
  • Chronic Interstitial Lung Disease associated with bilateral pulmonary infiltrates
  • Lung biopsy or resection on current admission
  • Immunosuppression caused by

    • neutropenia [i.e., polymorphonuclear leukocyte count < 1,000/μL (1 x 1012/L)] after chemotherapy or bone marrow transplantation for hematologic cancers
    • corticosteroid or cytotoxic therapy for a nonmalignant disease
    • the acquired immunodeficiency syndrome
  • Inability to wean from prone positioning or inhaled nitric oxide
  • Pregnancy or morbid obesity (body mass index >40 kg/m2)
  • Enrollment in another interventional study
  • Crossover from the CMV-group to the HFO-TGI-group at > 72 h after the onset of the severe oxygenation disturbances
  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: NCT00637507

Locations
Greece
Department of Intensive Care Medicine, Evaggelismos Hospital
Athens, Attica, Greece, GR-10675
University General Hospital of Larissa
Larissa, Thessaly, Greece, GR-41110
Sponsors and Collaborators
University of Athens
University of Thessaly
Investigators
Principal Investigator: Spyros D Mentzelopoulos, MD, PhD University of Athens Medical School, Athens, Greece
Principal Investigator: Sotiris Malachias, MD Department of Intensive Care Medicine, Evaggelismos Hospital, Athens, Greece
Study Director: Spyros G Zakynthinos, MD, PhD University of Athens Medical School, Athens, Greece
Study Chair: Charis Roussos, MD, PhD University of Athens Medical School, Athens, Greece
  More Information

Publications:
Mentzelopoulos SD, Malachias S, Tzoufi M, Markaki V, Zervakis D, Pitaridis M, Zakynthinos S. High frequency oscillation and tracheal gas insufflation for severe acute respiratory distress syndrome [abstract]. Intensive Care Med 2007;33(Suppl 2):S142

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Spyros D. Mentzelopoulos, Assistant Professor of Intensive Care Medicine, University of Athens
ClinicalTrials.gov Identifier: NCT00637507     History of Changes
Other Study ID Numbers: HFO-TGI-728-4-10-07
Study First Received: March 4, 2008
Last Updated: June 21, 2014
Health Authority: Greece: Ministry of Health and Welfare

Keywords provided by University of Athens:
High-Frequency Ventilation
Tracheal Gas Insufflation
Respiration, Artificial
Respiratory Distress Syndrome
Adult

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

ClinicalTrials.gov processed this record on November 20, 2014