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Variable Ventilation During Acute Respiratory Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Boston Medical Center
Sponsor:
Collaborator:
Wallace H. Coulter Foundation
Information provided by (Responsible Party):
Boston Medical Center
ClinicalTrials.gov Identifier:
NCT01083277
First received: September 18, 2009
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

Acute respiratory failure requiring support with mechanical ventilation occurs with an incidence of 77-100 per 100,000 person-years and accounts for half of all patients admitted to the intensive care unit. Major causes of acute respiratory failure include pneumonia, asthma, emphysema, and acute lung injury. These causes of acute respiratory failure may result in partial lung collapse (atelectasis), and airway narrowing (bronchoconstriction)that result in decreased oxygen levels requiring support with the ventilator. The prolonged inactivity in the supine position associated with mechanical ventilation can further result in atelectasis requiring increased oxygen supplementation through the ventilator.

The current standard of care in acute respiratory failure is a strategy of mechanical ventilation using a single lung volume delivered repeatedly. However, the current standard mechanical ventilation strategy is not consistent with the variability in respiration of healthy humans and has been shown to contribute to increased lung injury in some studies. The mortality associated with acute respiratory failure is high, 30-40%. Thus, improvements in mechanical ventilation strategies that improve oxygen levels and potentially decrease further lung injury delivered by the ventilator are warranted.

Recent studies by BU Professor Bela Suki and others in humans and animals with acute lung injury, bronchoconstriction, and atelectasis have shown that varying the lung volumes delivered by a ventilator significantly decreases biomarkers of lung injury, improves lung mechanics, and increases oxygenation when compared to identical mean volumes of conventional, monotonous low lung volume ventilation.

Therefore, we propose a first-in-human, Phase I study to evaluate the safety of this novel mode of ventilation, Variable Ventilation, during acute respiratory failure


Condition Intervention Phase
Acute Respiratory Failure
Device: variable ventilation
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Variable Ventilation During Acute Respiratory Failure

Resource links provided by NLM:


Further study details as provided by Boston Medical Center:

Primary Outcome Measures:
  • The occurrence of adverse events in the use of variable ventilation versus conventional ventilation, including the loss of any of the following (1) hemodynamic stability, (2) respiratory stability,(3) acid-base stability, and (4) neurological stability. [ Time Frame: Up to 24 hours after the end of the study period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Oxygenation [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    PaO2


Other Outcome Measures:
  • Biomarkers of lung injury [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    IL6, IL8, IL1Ra, SP-D, sTNFaR I and II

  • Lung mechanics [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    quasi static lung compliance, mean airway pressure, peak airway pressure, plateau pressure.

  • Sedatives [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
    need for increased sedative

  • PaCO2 [ Time Frame: 3 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: September 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: variable ventilation
A novel means of conducting mechanical ventilation that involves an approximately 40% variation in tidal volume around a set mean tidal volume
Device: variable ventilation
In variable ventilation, the tidal volume on the Puritan-Bennett 840 ventilator will be randomly varied by 40% on a breath-by-breath basis around a pre-set mean, using the variable ventilation software developed by Dr. Bela Suki and Dr. Arnab Majumdar. In conventional ventilation, the tidal volume on the Puritan-Bennett 840 ventilator will be set to equal the mean tidal volume used in variable ventilation and does not vary.
conventional ventilation
This is the control arm of the study, in which tidal volume will be set as the patient's baseline tidal volume prior to study entry and will not vary.
Device: variable ventilation
In variable ventilation, the tidal volume on the Puritan-Bennett 840 ventilator will be randomly varied by 40% on a breath-by-breath basis around a pre-set mean, using the variable ventilation software developed by Dr. Bela Suki and Dr. Arnab Majumdar. In conventional ventilation, the tidal volume on the Puritan-Bennett 840 ventilator will be set to equal the mean tidal volume used in variable ventilation and does not vary.

  Eligibility

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

Inclusion criteria

  1. Age > or equal to 18
  2. Requires mechanical ventilation using a volume-controlled mode.
  3. Admitted to Boston Medical Center Surgical, Medical, or Coronary Intensive Care Unit
  4. Evidence of impaired oxygenation on mechanical ventilator defined by PaO2/FiO2 ratio less than 350 (corresponding to an A-a gradient of approximately 100) or SatO2/FiO2 ratio less than 358 (requiring O2 saturation less than or equal to 97%).
  5. Meets "Clinical Stability Criteria" (on maximum of one vasopressor medication) for at least one hour prior to start of study protocol:

5a. Hemodynamically stable: mean arterial pressure greater than 60 mmHg, heart rate greater than 50 and less than 130 bpm 5b. Respiratory system stable: Respiratory rate less than 35 bpm, O2 saturation greater than 88%, peak pressure on ventilator less than 40 cm H20, FiO2 not greater than 0.80, PEEP level not greater than 12.5 cm H2O, requires suctioning less than once hourly.

5c. Acid-base stability: pH greater than 7.2 and less than 7.55 5d. Neurologic system stable: No agitation as defined by a Riker SAS Score between 2 (very sedated) and 4 (calm and cooperative) 6. Assent of primary ICU care team

Exclusion Criteria

  1. Do not resuscitate order
  2. Increased intracranial pressure
  3. Pregnancy (urine pregnancy test for all women of child-bearing age)
  4. Planned transport out of ICU during planned study protocol
  5. Coagulopathy (INR > 2.0 or PTT > 50)
  6. Severe thrombocytopenia (platelets < 20,000)
  7. Patients receiving medications meant to increase oxygenation such as inhaled nitric oxide, inhaled prostacyclin, intravenous prostacyclin, and intravenous treprostinil
  8. Any patient receiving a medication that is not consistent with FDA-approved labeling
  9. A change in the Riker SAS during the study protocol that results in a Riker SAS score of 1: "Unarousable" (minimal or no response to noxious stimuli, does not communicate or follow commands) or 5: "Agitation" (anxious or physically agitated, calms to verbal instructions) for a duration of greater than 15 minutes
  10. A Riker SAS of 6: "Very agitated" (requiring restraint and frequent verbal reminding of limits, biting ETT) or higher will result in immediate study discontinuation for the individual participant
  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: NCT01083277

Contacts
Contact: Allan Walkey, MD, MSc 617-638-4860 allan.walkey@bmc.org

Locations
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Allan Walkey, MD    617-638-4860    allan.walkey@bmc.org   
Sponsors and Collaborators
Boston Medical Center
Wallace H. Coulter Foundation
Investigators
Principal Investigator: George T O'Connor, MD Boston University
  More Information

No publications provided

Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT01083277     History of Changes
Other Study ID Numbers: H-27864
Study First Received: September 18, 2009
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Boston Medical Center:
oxygenation
ventilation
tidal volume
patterns of breathing
variable ventilation
mechanical ventilation

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Adult
Respiratory Insufficiency
Lung Diseases
Respiration Disorders
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 25, 2014