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Variable Ventilation During Acute Respiratory Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01083277
Recruitment Status : Terminated (Slow enrollment)
First Posted : March 9, 2010
Last Update Posted : July 11, 2017
Wallace H. Coulter Foundation
Information provided by (Responsible Party):
Allan J. Walkey, Boston Medical Center

Brief Summary:

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 or disease Intervention/treatment Phase
Acute Respiratory Failure Device: variable ventilation Other: Conventional ventilation Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Device Feasibility
Official Title: Variable Ventilation During Acute Respiratory Failure
Study Start Date : September 2012
Actual Primary Completion Date : July 2016
Actual Study Completion Date : December 23, 2016

Arm Intervention/treatment
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.
Other: Conventional ventilation
tidal volume will be set as the patient's baseline tidal volume prior to study entry and will not vary.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Oxygenation [ Time Frame: 3 hours ]

Other Outcome Measures:
  1. Biomarkers of lung injury [ Time Frame: 3 hours ]
    IL6, IL8, IL1Ra, SP-D, sTNFaR I and II

  2. Lung mechanics [ Time Frame: 3 hours ]
    quasi static lung compliance, mean airway pressure, peak airway pressure, plateau pressure.

  3. Sedatives [ Time Frame: 3 hours ]
    need for increased sedative

  4. PaCO2 [ Time Frame: 3 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01083277

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United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Wallace H. Coulter Foundation
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Principal Investigator: George T O'Connor, MD Boston University
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Responsible Party: Allan J. Walkey, BMC Attending Physician, Boston Medical Center Identifier: NCT01083277    
Other Study ID Numbers: H-27864
First Posted: March 9, 2010    Key Record Dates
Last Update Posted: July 11, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Allan J. Walkey, Boston Medical Center:
tidal volume
patterns of breathing
variable ventilation
mechanical ventilation
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiratory Distress Syndrome, Adult
Respiration Disorders
Respiratory Tract Diseases
Lung Diseases