Biomarkers of Lung Injury With Low Tidal Volume Ventilation Compared With Airway Pressure Release Ventilation

This study has suspended participant recruitment.
(pending further funding)
Sponsor:
Information provided by (Responsible Party):
Allan J. Walkey, Boston Medical Center
ClinicalTrials.gov Identifier:
NCT01038531
First received: December 22, 2009
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. Current evidence-based care of ALI consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further stretch-induced lung injury exacerbated by the ventilator. However, this strategy has been shown to be associated with increased lung injury in a subset of patients and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, non-experimental strategy of mechanical ventilation currently in routine clinical use. APRV is a pressure-cycled ventilator mode that allows a patient a greater degree of autonomy in controlling his or her breathing pattern than ARDSNet ventilation. Use of APRV has been associated with better oxygenation, less sedative usage, and less ventilator-associated pneumonia in small studies compared with other ventilator modes. However, debate exists over whether APRV might result in decreased or increased ventilator-associated lung injury when compared with ARDSNet ventilation. We intend to implement a randomized, cross over study looking at biomarkers of lung injury in patients with acute lung injury during ventilation with APRV and using the ARDSNet protocol. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.


Condition Intervention
Acute Lung Injury
Adult Respiratory Distress Syndrome
Other: low-tidal-volume ventilation
Other: APRV

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Biomarkers of Lung Injury With Low Tidal Volume Ventilation Compared With Airway Pressure Release Ventilation

Resource links provided by NLM:


Further study details as provided by Boston Medical Center:

Primary Outcome Measures:
  • The study will be powered to detect a decrease in plasma IL-6 levels (pg/ml) from ARDSNet to APRV [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in dose of sedation medications [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Riker score [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Lung mechanics [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Oxygenation with APRV versus ARDSNet [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: July 2010
Estimated Study Completion Date: September 2013
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: low-tidal-volume ventilation
Goal tidal volume is 6 cc/kg ideal body weight.
Other: low-tidal-volume ventilation
goal tidal volume of 6 cc/kg ideal body weight
Experimental: APRV
APRV allows spontaneous breathing.
Other: APRV
APRV is a time cycled, inverse-ratio, pressure controlled strategy that allows spontaneous breathing through the respiratory cycle.

Detailed Description:

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. The current evidence-based care consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further lung injury from overstretch of the lung induced by the ventilator. However, this strategy has been shown to be associated with continued lung injury in some studies and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, nonexperimental strategy of mechanical ventilation currently in routine clinical use. APRV allows a patient a greater degree of autonomy in controlling his/her breathing while achieving a higher mean airway pressure (at similar plateau pressures) than that typically achieved with ARDSNet. APRV has been associated with less ventilator-associated pneumonia, better oxygenation, and less sedative usage in small studies when compared with other methods of ventilation. However, debate exists over net effects of APRV with regard to ventilator-associated lung injury. Additionally, we recently completed a study showing that APRV was associated with lower ventilator associated pneumonia (VAP) rates, but this benefit did not appear to be mediated by sedation differences. We hypothesized that the VAP benefits might be mediated by greater lung recruitment and possibly less ventilator-induced lung injury with APRV. We propose a randomized, crossover study looking at biomarkers of lung injury in patients with acute lung injury ventilated with APRV and ARDSNet. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > or equal to 18.
  • On mechanical ventilation using a volume-controlled mode.
  • Admitted to Boston Medical Center Surgical, Medical, or Coronary Intensive Care Unit.
  • Meets American-European Consensus Criteria for Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome.
  • Required mechanical ventilator for less than 14 days.
  • Met ARDS or ALI criteria for less than 7 days prior to enrollment.
  • Assent of primary care team

Exclusion Criteria:

  • Do not resuscitate order.
  • Increased intracranial pressure.
  • Pregnancy (urine pregnancy test for all women of child-bearing age).
  • Planned transport out of ICU during planned study protocol.
  • Coagulopathy (INR>2.0 or PTT >50).
  • Severe thrombocytopenia (platelets <20,000).
  • History of obstructive lung disease (asthma and/or COPD).
  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: NCT01038531

Locations
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Investigators
Principal Investigator: George O'Connor, MD Boston University Medical College
  More Information

No publications provided

Responsible Party: Allan J. Walkey, Assistant Professor of Medicine, Boston Medical Center
ClinicalTrials.gov Identifier: NCT01038531     History of Changes
Other Study ID Numbers: H-28944
Study First Received: December 22, 2009
Last Updated: September 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Boston Medical Center:
Acute lung injury (ALI)
Adult respiratory distress syndrome (ARDS)
Low-tidal-volume strategy
ARDS Net
airway pressure release ventilation (APRV)
biomarkers of lung injury

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

ClinicalTrials.gov processed this record on September 18, 2014