The Use of High Frequency Oscillations With NIV in Hypercapnic COPD Participants

The Use of High Frequency Oscillations With Noninvasive Ventilation (NIV) in Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) Participants

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world, being the fourth leading cause of death in the world.

This study is designed to detect COPD participants with Expiratory Flow Limitation. EFL occurs when the airways become compressed which usually results when a pressure outside the airway exceeds the pressure inside the airway.

Participants will undergo study eligibility procedures at visit 1. At visit 2 participants will undergo a baseline auto-EPAP (Expiratory Positive Airway Pressure) measurement. Then the order will be randomized to three different treatment methods. Between each treatment there will be at least a 10 minute washout period in order for CO2 to stabilize and return to baseline.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: BiPAP Synchrony ventilator

Detailed Description

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world, being the fourth leading cause of death in the world.

COPD is a disease that results in varying degrees of dyspnea, or shortness of breath. Spirometry is a method of diagnosing COPD with the presence of a post bronchodilator FEV1 <80% of the predicted value in combination with an FEV1 / FVC <70%. This would confirm that there is a presence of airflow limitation that is not fully reversible.

The presence of airflow limitation has been identified as one of the main causes of dyspnea in patients with chronic obstructive pulmonary disease (1). Expiratory Flow Limitation (EFL) occurs when the airways become compressed which usually results when a pressure outside the airway exceeds the pressure inside the airway. As an airflow obstruction worsens, EFL appears at much lower flows for a given lung volume and it becomes present at rest or at least develops early during exercise (2).

Early detection of EFL consisted of either invasive balloon catheterization or relatively complex plethysmographic techniques. An alternative approach, and one that will be used in this study, involves utilizing the Forced Oscillation Technique (FOT).

Alternatively High Frequency Oscillations (HFO) has shown to effectively lower CO2 levels, but traditionally require intubation or a trans tracheal catheter. Treatment with a specialized noninvasive ventilator is possible and it is proposed that therapy can be augmented by the application of an optimized EPAP to splint open the lower airways in order to increase the diffusive capabilities of the high frequency oscillations into lower alveolar regions. There are approximately 25 million hypercapnic patients with EFL that could benefit from this therapy. High frequency oscillations integrated into a specialized noninvasive ventilator has the advantages of lower cost than other solutions and significantly lower medical risks. In addition, high frequency oscillation uses lower pressures to achieve effective therapy which means less chance of barotrauma and greater patient acceptance.

This study will enroll subjects at a screening visit. Screening will include a physical exam and vital signs, pregnancy test (if applicable), questionnaires, pulse oximetry, measure of carbon dioxide levels, determination of EFL by an auto- Expiratory Positive Airway Pressure (EPAP) ventilator, and spirometry.

If the patient is eligible and tolerates the above procedures, they will be asked to complete an in home-based sleep study prior to visit 2. Alice Night One/ Alice PDX are portable home sleep testing devices that record information about breathing.

At visit 2 participants will be monitored continuously via a 3 lead EKG, oxygen saturation by pulse oximetry (SPO2), Carbon Dioxide concentration(TcCO2) monitor, RespiTrace belt and ventilator data.

During Visit 2, participants will first undergo a repeat optimal EPAP determination and then trial 3 different sessions of High Frequency Oscillation (HFO) therapy for 20 minutes with at least a 10 minute wash out period between each session to allow the participant's CO2 to stabilize or return to baseline. The order of the sessions will be randomized for each patient. Participants will be placed in a semi-recumbent position and wear a nasal CPAP mask for each session. A TcCO2 monitor patch will be placed on the skin (forehead area) to collect carbon dioxide measurements during each session. A RespiTrace belt will placed on the participants' chest wall to measure chest wall and diaphragmatic excursion during each session. A 3 lead EKG will also be used to monitor cardiac activity during each session.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 21 years of age; < 85 years of age
• Participants that have been physician diagnosed (primary diagnosis) with Obstructive Airway Disease (to include:Chronic Obstructive Pulmonary Disease (COPD); Bronchiectasis; Severe Asthma); forced expiratory volume in 1 second (FEV1) < 60% FEV1/ forced vital capacity (FVC) <60%
• Arterial CO2 > 45 mmHg as determined by blood gas (PaCO2) or transcutaneous (tcCO2) >50 within the past month
• Ability to provide consent
• Participant has not used Non-Invasive Ventilation (BiPAP/CPAP) therapy in the past 8 hours
• Participant has no child bearing potential OR a negative pregnancy test in a woman of childbearing potential

Exclusion Criteria:

• Participants that have not returned to their baseline health status from an exacerbation of COPD or other pulmonary problems or have not established at least two weeks of stability at a new baseline.
• Use of antibiotics or prednisone for a COPD exacerbation within the previous 4 weeks.
• Uncontrolled Hypertension
• Participants that require greater than 3 liters of oxygen at rest
• History of cardiovascular instability, including uncontrolled ventricular arrhythmias, angina, diastolic BP > 100 mmHg and all Participants with pacemakers
• Any major non-COPD uncontrolled disease or condition, such as congestive heart failure, malignancy, end-stage heart disease, liver or renal insufficiency (that requires current evaluation for liver or renal transplantation or dialysis), amyotrophic lateral sclerosis, or severe stroke, or other condition as deemed appropriate by investigator as determined by review of medical history and / or participant reported medical history
• History of pneumothorax
• Apnea Hypopnea Index (AHI) > 15 via in-home sleep study
• Excessive alcohol intake (> 6oz hard liquor, 48 oz. beer or 20 oz. wine daily), or illicit drug use by review of medical history and / or participant reported medical history
• Daily use of prescribed narcotics (greater than 30 mg morphine equivalent)
• History of Giant bullous emphysema
• A positive urine pregnancy test when screening for study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: optimal EPAP determination; On the BiPAP Synchrony ventilator the EPAP (and IPAP) will be automatically adjusted by the ventilator to find optimal EPAP that abolishes EFL. Peak-to-Peak pressure oscillations will be set at 2.5 cmH2O (centimeters of water)	Device: BiPAP Synchrony ventilator; The BiPAP Synchrony ventilator will be used to determine Expiratory Positive Airway Pressure (EPAP). The ventilator will be used with varying pressure supports and oscillations depending on what arm of the study the participant is in.
Experimental: Optimized EPAP w/ no peak-to-peak; On the BiPAP Synchrony ventilator the EPAP (and IPAP) will be set at optimal pressure as determined by the Auto EPAP. Peak-to-Peak pressure oscillations will be set at 0 cmH2O (centimeters of water)	Device: BiPAP Synchrony ventilator; The BiPAP Synchrony ventilator will be used to determine Expiratory Positive Airway Pressure (EPAP). The ventilator will be used with varying pressure supports and oscillations depending on what arm of the study the participant is in.
Experimental: Optimized EPAP w/ max peak-to-peak; On the BiPAP Synchrony ventilator EPAP (and IPAP) will be set at optimal pressure as determined by the Auto EPAP. Peak-to-Peak pressure oscillations will be set at 5 cmH2O (centimeters of water)	Device: BiPAP Synchrony ventilator; The BiPAP Synchrony ventilator will be used to determine Expiratory Positive Airway Pressure (EPAP). The ventilator will be used with varying pressure supports and oscillations depending on what arm of the study the participant is in.
Experimental: non-optimized EPAP w/ no peak-to-peak; On the BiPAP Synchrony ventilator EPAP will be set at 4 cmH2O and IPAP will be set at 10 cmH2O (centimeters of water). Peak-to-Peak pressure oscillations will be set at 0 cmH2O (centimeters of water).	Device: BiPAP Synchrony ventilator; The BiPAP Synchrony ventilator will be used to determine Expiratory Positive Airway Pressure (EPAP). The ventilator will be used with varying pressure supports and oscillations depending on what arm of the study the participant is in.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbon Dioxide Levels	Transcutaneous carbon dioxide (TcCO2) monitoring is a non-invasive alternative to arterial blood sampling. Carbon Dioxide Levels will be measured for each participant as they complete each arm.	Baseline and 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Rate	Minute ventilation in regards to respiratory rate and volume of gas exchanged will be measured for each participant as they complete each arm.	20 minutes
Tidal Volume	Minute ventilation in regards to volume of gas exchanged will be measured for each participant as they complete each arm.	20 minutes
Minute Ventilation for Carbon Dioxide	Minute Ventilation in regards to the diffusion state of the lungs and carbon dioxide will be measured for each participant as they complete each arm.	20 minutes

Collaborators and Investigators

• Sponsor: Philips Respironics
• Collaborators: University of Pittsburgh Medical Center
• Investigators: Principal Investigator: Frank Sciurba, MD, University of Pittsburgh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2015
• Primary Completion (Actual): August 24, 2016
• Study Completion (Actual): August 24, 2016

Study Registration Dates

• First Submitted: February 9, 2016
• First Submitted That Met QC Criteria: February 9, 2016
• First Posted (Estimate): February 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 6, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Biphasic Continuous Positive Airway Pressure; High-Frequency Ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: HRC-1433-HFO-SS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are no plans to share individual participant data (IPD), only aggregate data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No