Clinical trial NCT02680639: The Use of High Frequency Oscillations With NIV in Hypercapnic COPD Participants
Official title: The Use of High Frequency Oscillations With Noninvasive Ventilation (NIV) in Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) Participants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: High-Frequency Ventilation
Biphasic Continuous Positive Airway Pressure
Lead sponsor: Philips Respironics
Sponsor class: INDUSTRY
Collaborators: name: University of Pittsburgh Medical Center
First posted: 2016-02-11
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Carbon Dioxide Levels
timeFrame: Baseline and 20 minutes
Secondary outcomes:
measure: Respiratory Rate
timeFrame: 20 minutes
measure: Tidal Volume
timeFrame: 20 minutes
measure: Minute Ventilation for Carbon Dioxide
timeFrame: 20 minutes
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Frank Sciurba, MD
role: PRINCIPAL_INVESTIGATOR
References: