Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
The study evaluates the safety and efficacy of the modified Bi-level positive airway pressure (BiPAP) A40 with Vector Algorithm to treat Chronic Obstructive Pulmonary Disease (COPD) patients with excessive carbon dioxide in their bloodstream (hypercapnia) and expiratory flow limitation (EFL), a constriction of the lower airways. The study will include current users of non-invasive ventilation (NIV) as well as those who are not currently using an NIV device.
Detailed description
This study is a prospective randomized controlled cross-over pilot trial to investigate the clinical efficacy and safety of the Modified Bi-level positive airway pressure (BiPAP) A40 with Vector Algorithm (Vector Device), a non-invasive ventilation (NIV) device, to treat Chronic Obstructive Pulmonary Disease (COPD). Approximately 30 COPD patients with chronic hypercapnia and evidence of expiratory flow limitation (EFL) will be included. It is estimated that 50 patients may need to be enrolled in order to complete 30. There will be two different patient cohort groups, patients that are current users of NIV and patients that are Naïve to NIV. Only those that meet the inclusion/exclusion criteria will be screened to determine if EFL is present. If participants are found to have EFL they will undergo a 20 minute EFL abolishment determination. Those participants that have EFL and a titrated expiratory positive airway pressure (EPAP) ≥6cmH2O will be scheduled for study visit 2. During study visit 2, participants will be randomized in a 1:1 ratio to receive either standard NIV (control) or Vector (Active) for the first 4 to 6-week at-home treatment period, followed by the other treatment during the second 4 to 6 weeks. Participants will have up to 4 (NIV current Users) or 5 (NIV Naïve) in-person visits that will include 2 overnight sleep studies with polysomnogram (PSG).
Interventions
DEVICEModified BiPAP A40 with Vector Algorithm (Vector)
The Modified BiPAP A40 with Vector Algorithm (Vector) is intended to provide non-invasive ventilatory support to treat patients weighing over 10 kg (22 lbs) with Obstructive Sleep Apnea (OSA) or Respiratory Insufficiency. It is intended to be used within the home, institutional/ hospital, and diagnostic laboratory environments. This device is not intended for life support. The BiPAP A40 EFL screening and therapy is intended for patients weighing over 30 kg (66 lbs) with Obstructive Sleep Apnea (OSA), or Respiratory Insufficiency with primary cause being Chronic Obstructive Pulmonary Disease (COPD) to screen for the presence, and abolishment of Expiratory Flow Limitation (EFL).
DEVICEModified BiPAP A40 with Standard of Care Settings
The Modified BiPAP A40 with Standard of Care settings is intended to provide non-invasive ventilatory support to treat patients weighing over 10 kg (22 lbs) with Obstructive Sleep Apnea (OSA) or Respiratory Insufficiency. It is intended to be used within the home, institutional/ hospital, and diagnostic laboratory environments. This device is not intended for life support. The BiPAP A40 EFL screening and therapy is intended for patients weighing over 30 kg (66 lbs) with Obstructive Sleep Apnea (OSA), or Respiratory Insufficiency with primary cause being Chronic Obstructive Pulmonary Disease (COPD) to screen for the presence, and abolishment of Expiratory Flow Limitation (EFL).
Sponsors
Philips Clinical & Medical Affairs Global
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients who meet inclusion criteria will be randomized in a 1:1 ratio to receive either standard non-invasive ventilation (NIV) (control) or Vector (Active) for the first 4 to 6-week treatment period, followed by the other treatment during the second 4 to 6 weeks (see figure 1). There will be two different patient cohort groups, patients that are current users of NIV and patients that are Naïve to NIV.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 40 years of age; less than or equal to 80 years of age 2. Ability to provide consent 3. Chronic obstructive pulmonary disease (COPD) patients with hypercapnia (as defined as greater than or equal to 52mmHg) who are either current non-invasive ventilation (NIV) users or naïve to NIV 4. On average, use NIV more than 4 hours per night (Current NIV users). 5. Must present with expiratory flow limitation (EFL) via screening of the Vector device at 3 cmH2O 6. Have an EPAP to abolish EFL greater or equal to 6cmH2O
Exclusion criteria
1. Any major non-COPD uncontrolled disease or condition, such as congestive heart failure, malignancy, 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 2. Suffering from a COPD exacerbation (Defined as hospital admission, ER/urgent care visit, MD visit with medication change or other intervention deemed to be clinically significant by the investigator at the time of data collection or in the 14 days prior to data collection 3. Self-reported Pregnancy or positive pregnancy test for women of childbearing potential. 4. Employee or family member that is affiliated with Philips 5. Currently employed by a manufacturer of respiratory products or family member employed by a manufacturer of respiratory products 6. Any history of giant bulla (size \>1/3 hemi-thorax) 7. History of pneumothorax \< 6 months 8. Participants currently using a PAP or NIV device at home with a documented EPAP setting on their current device that is greater than the calculated EPAP determined during the therapy session of the screening visit (Current NIV Users). 9. Life expectancy ≤12 months as determined by clinical investigator 10. Low BP: Systolic \<90 11. Recent cranial surgery (i.e, less than 1 year) 12. Impaired swallowing as reported by participant or diagnostic exam 13. Recent upper airway or GI surgery within the past 6 months 14. Unable to be fitted with mask 15. Excessive secretions as reported by clinical investigator/physician assessment, inability to maintain a patent airway or adequately clear secretions, or at risk for aspiration of gastric contents 16. Diagnosed with acute sinusitis or otitis media 17. Epistaxis, causing pulmonary aspiration of blood 18. Existing respiratory failure 19. Participants who are naïve to NIV (Cohort 2) that use the device fewer than 3 out of 7 nights during the second week of the 2-week acclimation period 20. Participants who are naïve to NIV (Cohort 2) that average less than 4 hours of device use during the second week of the 2-week acclimation period 21. Participants who are naïve to NIV (Cohort 2) with an average nightly 90% EPAP pressure during the second week of the 2-week acclimation period that is higher than the titrated EFL EPAP pressure determined at the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daytime PaCO2 (Arterial Blood Gas) | At the end of the 4-to-6-week period | Room air CO2 levels at the end of 4-6 weeks of therapy as determined by Arterial Blood Gas (PaCO2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average 30 Day Ventilator Usage Hours | Up to 30 days of device use | How many hours per night over 30 days that the participant uses the device. |
| Patient Comfort and Therapy Preference Based Questionnaire Responses | Up to 30 days of device use | Comfort data from device satisfaction/preference questionnaire after 30 days of device use. The specific question analyzed was Which ventilator pressure settings or therapy did you prefer? Outcome was number of participants who selected each therapy as preferred. |
| Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) Assessment | Up to 30 days of device use | Incidence of Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) for the Vector vs. the control group. |
Countries
United States
Participant flow
Pre-assignment details
21 participants were consented and screened. 12 participants were screen failures, one of these participants was rescreened and determined to be eligible resulting in 10 participants being enrolled and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Participants All participants that were enrolled and randomized. | 10 |
| Screen Fails All participants that were screen failed. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Randomized Participants | Screen Fails |
|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 7.5 | 63.0 years STANDARD_DEVIATION 8.4 | 70.1 years STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 10 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 21 participants | 10 participants | 11 participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 2 / 10 | 2 / 10 |
| serious Total, serious adverse events | 3 / 10 | 0 / 10 |
Outcome results
Primary
Daytime PaCO2 (Arterial Blood Gas)
Room air CO2 levels at the end of 4-6 weeks of therapy as determined by Arterial Blood Gas (PaCO2)
Time frame: At the end of the 4-to-6-week period
Population: 10 participants were randomized, 2 participants received Standard of care for both arms, so they were excluded from analysis, 2 additional participants discontinued prior to completing both arms and they were excluded from the analysis. 1 participant did not contribute PaCO2 data. No NIV naive participants were enrolled.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vector Device (NIV Current Users) | Daytime PaCO2 (Arterial Blood Gas) | 59.2 mmHG | Standard Deviation 16.6 |
| Standard of Care NIV (NIV Current Users) | Daytime PaCO2 (Arterial Blood Gas) | 49.8 mmHG | Standard Deviation 8.8 |
Secondary
Average 30 Day Ventilator Usage Hours
How many hours per night over 30 days that the participant uses the device.
Time frame: Up to 30 days of device use
Population: Processed data was only available N=3 participants. Average adherence was calculated among all days in the time period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vector Device (NIV Current Users) | Average 30 Day Ventilator Usage Hours | 7.58 hours | Standard Deviation 4.52 |
| Standard of Care NIV (NIV Current Users) | Average 30 Day Ventilator Usage Hours | 7.40 hours | Standard Deviation 3.38 |
Secondary
Patient Comfort and Therapy Preference Based Questionnaire Responses
Comfort data from device satisfaction/preference questionnaire after 30 days of device use. The specific question analyzed was Which ventilator pressure settings or therapy did you prefer? Outcome was number of participants who selected each therapy as preferred.
Time frame: Up to 30 days of device use
Population: 10 participants were randomized, 2 participants received Standard of care for both arms, and they were excluded from analysis, 2 additional participants discontinued prior to completing both arms and they were excluded from the analysis. The 6 participants answered comparative survey after completing both arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vector Device (NIV Current Users) | Patient Comfort and Therapy Preference Based Questionnaire Responses | 3 Participants |
| Standard of Care NIV (NIV Current Users) | Patient Comfort and Therapy Preference Based Questionnaire Responses | 3 Participants |
Secondary
Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) Assessment
Incidence of Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) for the Vector vs. the control group.
Time frame: Up to 30 days of device use
Population: Frequency of USADEs or SAEs when participant was using the assigned treatment. All SAEs which occurred were determined to be unrelated to the device. The term incidence in the protocol endpoint was imprecise. Frequency is the more appropriate term.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vector Device (NIV Current Users) | Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) Assessment | 3 Participants |
| Standard of Care NIV (NIV Current Users) | Unanticipated Serious Adverse Device Effects (USADEs) and Serious Adverse Events (SAEs) Assessment | 0 Participants |