Comparison of Two Methods of High Frequency Oscillatory Ventilation in Individuals With Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Acute respiratory distress syndrome (ARDS) is a severe lung condition that causes respiratory failure. Individuals with ARDS often require the use of an artificial breathing machine, known as a mechanical ventilator. High frequency oscillatory ventilation (HFOV) is a form of mechanical ventilation that pumps small amounts of air into the lungs at a constant high rate. The purpose of this study is to compare the safety and efficacy of two HFOV methods in individuals with ARDS.

Detailed Description
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ARDS is a serious condition that involves lung inflammation and fluid accumulation in the air sacs, leading to low blood oxygen levels and respiratory failure. It is often fatal and affects approximately 160,000 individuals each year in the United States. The main form of treatment for ARDS is delivery of oxygen and a continuous level of pressure to the damaged lungs through mechanical ventilation. However, some methods of mechanical ventilation may cause ventilator-associated lung injury (VALI), a condition that can result from overdistension of the lungs during inspiration or from excessive mechanical forces. VALI can delay or prevent healing from respiratory failure. HFOV is a mechanical ventilation method that pumps small amounts of air into the lungs at a constant high rate. Because the increments of air are small the likelihood of experiencing overdistension and developing VALI may be reduced. While HFOV is an effective, commonly used ventilation method, there have been no studies that demonstrate the efficacy of HFOV in comparison to the efficacy of conventional mechanical ventilation methods. This study will compare two different HFOV techniques: the HFOV-Hi method, which uses higher airway pressure, and the HFOV-Lo method, which uses lower airway pressure. The purpose of this study is to compare the safety and efficacy of HFOV-Hi, HFOV-Lo, and standard mechanical ventilation methods in individuals with ARDS. This study will enroll individuals with ARDS at four Baltimore hospitals. Participants will be randomly assigned to receive either HFOV-Hi or HFOV-Lo. All participants will receive their assigned HFOV method for 7 days, until spontaneous breathing occurs, or until death, whichever occurs first. Blood collected at baseline and Days 1 and 3 will be analyzed for markers of inflammation and lung injury. Participants' clinical status will be monitored until they no longer need ventilation and return home, or for up to 60 days while in the hospital. Individuals being treated for ARDS at the participating hospitals who decline to enroll in the study will be asked for permission to monitor their medical progress. These individuals will not take part in any study procedures, but their clinical information will be used for comparison purposes. Additionally, clinical information on other ARDS patients admitted to the hospital over the previous 2 years will be analyzed.

Official Title
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Phase II Clinical Trial of Two Approaches to High Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome

Conditions
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Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Procedure: High Frequency Oscillatory Ventilation-Hi
* Procedure: High Frequency Oscillatory Ventilation-Lo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute onset of all of the following criteria within a 24-hour period: Bilateral infiltrates consistent with edema on frontal chest radiograph, with a duration of no more than 7 days Requires positive pressure ventilation through an endotracheal tube PaO2/FiO2 less than 200 while receiving positive end-expiratory pressure (PEEP) at more than 8 cm H2O for at least 4 hours, with a duration of no more than 7 days No clinical evidence of left atrial hypertension Exclusion Criteria: Weighs less than 35 kilograms Receives more than 5 days of mechanical ventilation during current hospitalization Attending physician declines to give consent for participant to enroll Patient or surrogate declines or is unable to give consent Participation in another interventional study for ARDS in the 30 days prior to study entry Intracranial hypertension Single lung transplant Burns over more than 30% of the surface area of the body Pregnant Sickle (Hgb SS) or sickle-thal (Hgb SC) hemoglobin Pre-existing illness with a life expectancy of 6 months or less Physicians and family are not committed to full support (Exception: An individual will not be excluded if he/she would receive all medical care except for attempts at resuscitation from cardiac arrest) Severe chronic lung disease Prior lung resection More than 72 hours has passed since inclusion criteria were met

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HFOV-Lo<br>High Frequency Oscillatory Ventilation using lower mean airway pressures and higher FiO2s. | Procedure: High Frequency Oscillatory Ventilation-Lo<br>* HFOV will be conducted without routine recruitment maneuvers and with a table of mPaw and FiO2s that include relatively low mPaw's.<br>|
| Experimental: HFOV-Hi<br>High Frequency Oscillatory Ventilation using higher mean airway pressures | Procedure: High Frequency Oscillatory Ventilation-Hi<br>* HFOV will be conducted with recruitment maneuvers and with a table of mPaw and FiO2s that include higher mPaw's.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of ventilator free days |  | Measured at 28 days | 
| Changes in plasma concentration of IL-6 |  | Measured at 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of intensive care unit free days |  | Measured at 28 days | 
| Mortality |  | Measured at 60 days | 
| Number of hospital free days |  | Measured at 60 days | 
| Changes in plasma IL1ra |  | Measured at 3 days | 
| Changes in plasma IL-1 |  | Measured at 3 days | 
| Changes in plasma IL-10 |  | Measured at 3 days | 
| Changes in plasma surfactant protein D |  | Measured at 3 days | 
| Changes in plasma von Willebrand factor |  | Measured at 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Acute Lung Injury, Mechanical Ventilation, Lung