Study of a Novel Technique of Mechanical Ventilation in Patients With Severe Acute Respiratory Failure

NCT00637507 | Completed Phase 2 DMC

• 1 other identifier: HFO-TGI-728-4-10-07
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Respiratory Distress Syndrome

Keywords

High-Frequency Ventilation; Tracheal Gas Insufflation; Respiration, Artificial; Respiratory Distress Syndrome; Adult

Outcome Measures

Primary Outcomes (1)

• Survival to days 28 and 60 post-randomization, and to Hospital Discharge

  28 days to more than 60 days post-randomization

Secondary Outcomes (6)

• Lung recruitment during the study-intervention period

  8 days post-randomization

• Evolution of Gas-exchange, Hemodynamics, and Respiratory Mechanics during the Study Intervention Period

  8-10 days post-randomization

• Ventilator Free Days

  60 days post-randomization

• Organ or System Failure Free Days

  60 days post-randomization

• Occurrence of barotrauma (i.e., any new pneumothorax, pneumomediastinum, or subcutaneous emphysema, or pneumatocele > 2 cm)

  60 days post-randomization

Study Arms (2)

2

NO INTERVENTION

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.

1

EXPERIMENTAL

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

Interventions

High-frequency Oscillation and Tracheal Gas Insufflation OTHER

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).

Also known as: HFO-TGI

1

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Department of Intensive Care Medicine, Evaggelismos Hospital

Athens, Attica, GR-10675, Greece

Location

University General Hospital of Larissa

Larissa, Thessaly, GR-41110, Greece

Location

Related Publications (17)

• 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

• Brun-Buisson C, Minelli C, Bertolini G, Brazzi L, Pimentel J, Lewandowski K, Bion J, Romand JA, Villar J, Thorsteinsson A, Damas P, Armaganidis A, Lemaire F; ALIVE Study Group. Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med. 2004 Jan;30(1):51-61. doi: 10.1007/s00134-003-2022-6. Epub 2003 Oct 16.

  PMID: 14569423 BACKGROUND

• Esteban A, Anzueto A, Frutos F, Alia I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguia C, Nightingale P, Arroliga AC, Tobin MJ; Mechanical Ventilation International Study Group. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002 Jan 16;287(3):345-55. doi: 10.1001/jama.287.3.345.

  PMID: 11790214 BACKGROUND

• Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L, Latini R; Prone-Supine Study Group. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001 Aug 23;345(8):568-73. doi: 10.1056/NEJMoa010043.

  PMID: 11529210 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

• Mancebo J, Fernandez R, Blanch L, Rialp G, Gordo F, Ferrer M, Rodriguez F, Garro P, Ricart P, Vallverdu I, Gich I, Castano J, Saura P, Dominguez G, Bonet A, Albert RK. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006 Jun 1;173(11):1233-9. doi: 10.1164/rccm.200503-353OC. Epub 2006 Mar 23.

  PMID: 16556697 BACKGROUND

• Fessler HE, Derdak S, Ferguson ND, Hager DN, Kacmarek RM, Thompson BT, Brower RG. A protocol for high-frequency oscillatory ventilation in adults: results from a roundtable discussion. Crit Care Med. 2007 Jul;35(7):1649-54. doi: 10.1097/01.CCM.0000269026.40739.2E.

  PMID: 17522576 BACKGROUND

• Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. doi: 10.1097/00003246-200201000-00020. No abstract available.

  PMID: 11902253 BACKGROUND

• Murray MJ, Cowen J, DeBlock H, Erstad B, Gray AW Jr, Tescher AN, McGee WT, Prielipp RC, Susla G, Jacobi J, Nasraway SA Jr, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists, American College of Chest Physicians. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med. 2002 Jan;30(1):142-56. doi: 10.1097/00003246-200201000-00021. No abstract available.

  PMID: 11902255 BACKGROUND

• Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

  PMID: 10793162 BACKGROUND

• Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006 Apr 27;354(17):1775-86. doi: 10.1056/NEJMoa052052.

  PMID: 16641394 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

• Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976 Dec;34(6):585-612. doi: 10.1038/bjc.1976.220.

  PMID: 795448 BACKGROUND

• Geller NL, Pocock SJ. Interim analyses in randomized clinical trials: ramifications and guidelines for practitioners. Biometrics. 1987 Mar;43(1):213-23.

  PMID: 3567306 BACKGROUND

• Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. doi: 10.1056/NEJM199802053380602.

  PMID: 9449727 BACKGROUND

• 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

  RESULT

• 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 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Respiratory Aspiration

Interventions

High-Frequency Ventilation

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Spyros G Zakynthinos, MD, PhD

  University of Athens Medical School, Athens, Greece

  STUDY DIRECTOR

• Charis Roussos, MD, PhD

  University of Athens Medical School, Athens, Greece

  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 of Intensive Care Medicine

Study Record Dates

• First Submitted: March 4, 2008
• First Posted: March 18, 2008
• Study Start: March 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: November 21, 2016

Record last verified: 2016-11

Locations

GR (2)