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Variable Ventilation During Acute Respiratory Failure

Primary Purpose

Acute Respiratory Failure

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

variable ventilation

Conventional ventilation

About this trial

This is an interventional device feasibility trial for Acute Respiratory Failure focused on measuring oxygenation, ventilation, tidal volume, patterns of breathing, variable ventilation, mechanical ventilation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

Age > or equal to 18
Requires mechanical ventilation using a volume-controlled mode.
Admitted to Boston Medical Center Surgical, Medical, or Coronary Intensive Care Unit
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%).
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

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)
Patients receiving medications meant to increase oxygenation such as inhaled nitric oxide, inhaled prostacyclin, intravenous prostacyclin, and intravenous treprostinil
Any patient receiving a medication that is not consistent with FDA-approved labeling
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
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

Sites / Locations

Boston Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

variable ventilation

conventional ventilation

Arm Description

A novel means of conducting mechanical ventilation that involves an approximately 40% variation in tidal volume around a set mean tidal volume

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.

Outcomes

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.

Secondary Outcome Measures

Oxygenation

PaO2

Full Information

NCT ID

NCT01083277

First Posted

September 18, 2009

Last Updated

July 6, 2017

Sponsor

Boston Medical Center

Collaborators

Wallace H. Coulter Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01083277

Brief Title

Variable Ventilation During Acute Respiratory Failure

Official Title

Variable Ventilation During Acute Respiratory Failure

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Terminated

Why Stopped

Slow enrollment

Study Start Date

September 2012 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

December 23, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Boston Medical Center

Collaborators

Wallace H. Coulter Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Respiratory Failure

Keywords

oxygenation, ventilation, tidal volume, patterns of breathing, variable ventilation, mechanical ventilation

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

variable ventilation

Arm Type

Experimental

Arm Description

A novel means of conducting mechanical ventilation that involves an approximately 40% variation in tidal volume around a set mean tidal volume

Arm Title

conventional ventilation

Arm Type

Other

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

variable ventilation

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Conventional ventilation

Intervention Description

tidal volume will be set as the patient's baseline tidal volume prior to study entry and will not vary.

Primary Outcome Measure Information:

Title

Time Frame

Up to 24 hours after the end of the study period

Secondary Outcome Measure Information:

Title

Oxygenation

Description

PaO2

Time Frame

3 hours

Other Pre-specified Outcome Measures:

Title

Biomarkers of lung injury

Description

IL6, IL8, IL1Ra, SP-D, sTNFaR I and II

Time Frame

3 hours

Title

Lung mechanics

Description

quasi static lung compliance, mean airway pressure, peak airway pressure, plateau pressure.

Time Frame

3 hours

Title

Sedatives

Description

need for increased sedative

Time Frame

3 hours

Title

PaCO2

Time Frame

3 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria Age > or equal to 18 Requires mechanical ventilation using a volume-controlled mode. Admitted to Boston Medical Center Surgical, Medical, or Coronary Intensive Care Unit 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%). 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 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) Patients receiving medications meant to increase oxygenation such as inhaled nitric oxide, inhaled prostacyclin, intravenous prostacyclin, and intravenous treprostinil Any patient receiving a medication that is not consistent with FDA-approved labeling 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George T O'Connor, MD

Organizational Affiliation

Boston University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Boston Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Variable Ventilation During Acute Respiratory Failure

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