Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Ventilator, Constant work rate
Brief summary
Pilot study in 15 stable male subjects with severe-to-very severe Chronic Obstructive Pulmonary Disease (COPD) to evaluate the effects of short term use of the Breathe Technologies noninvasive open ventilation (NIOV) system on respiratory mechanics during constant work rate exercise in subjects with severe COPD.
Detailed description
Study was a randomized double-blinded crossover design in which subjects completed a series of exercises at a constant work rate while using 1) Test noninvasive ventilation (NIOV) system powered by compressed air, 2) Test NIOV system powered by 100% oxygen, 3) nasal cannula oxygen, 4) nothing (Control). Subjects were assessed during constant work rate exercise as reflected by exercise duration, isotime oxygenation (SpO2), and isotime dyspnea score (Borg). Exercise sessions took place over 4 visits with each visit lasting approximately 5 hours.
Interventions
DEVICENIOV - Room Air
Noninvasive ventilation with device powered by compressed room air.
DEVICENIOV - Oxygen
Noninvasive ventilation with device powered by compressed medical (100%) oxygen.
DEVICENasal Cannula Oxygen
Supplemental oxygen delivered using a standard nasal cannula connected to 100% medical oxygen.
Sponsors
Breathe Technologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Adult males, ≥ 40 years of age * Diagnosis of severe COPD (GOLD stage III or IV) defined as having a FEV1 \< 50% of predicted and an FEV1/FVC ratio \< 70% of predicted * Ventilatory limitation to exercise, documented by a VE/MVV \> 0.85 * SpO2 between 80% and 88% during incremental exercise testing on room air * Willingness and ability (after training) to exercise on a cycle ergometer * Willingness and ability to perform all other study related procedures and tasks * Ability to be properly fitted with the Breathe nasal mask * Ability to tolerate and be appropriately titrated on the Breathe ventilator (See Appendix E) * Ability to be properly fitted with an exercise mask * Fluency in written and spoken English * Provision of written informed consent
Exclusion criteria
* History of acute exacerbation of COPD within 30 days of screening * History of serious epistaxis within 14 days of screening * Requirement of \> 5 LPM nasal O2 to maintain an SpO2 \> 90% while at rest * History of pneumothorax secondary to lung bullae * History of intolerance to supplemental oxygen * Musculoskeletal or other non-pulmonary impairment that limits exercise tolerance * Inability to achieve an optimal CWR level (4-7 minutes) during Study Visit 1R * Current participation in another interventional study or participation within 14 days of screening * Presence of any condition or abnormality that in the opinion of the Principal Investigator may compromise the subject's safety or the quality of the study data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions | Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxygen and Nasal Cannula Oxygen. | Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SpO2 During Constant Workrate Exercise at Isotime | Outcome was measured in each of the Study day 1,2, 3 and 4. Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxyg | Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control). |
| Borg Dyspnea Score During Constant Workrate Exercise at Isotime | Outcome was measured in each Study day 1,2,3 and 4. Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxygen and N | Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control) at isotime. Borg Dyspnea Score ranges in values from 0 to 10. The lower score represent better outcome. 0 = No breathlessness at all, representing better outcome 10 = Maximum breathlessness, representing worse outcome |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Group Crossover design. Subject were randomized to complete all 4 study arms: 1) NIOV - Oxygen, 2) NIOV - Room Air, 3) Oxygen Nasal Cannula, 4) No treatment | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Overall Study Group |
|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions
Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control).
Time frame: Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxygen and Nasal Cannula Oxygen.
Population: Per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIOV - Room Air | Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions | 6.3 minutes | Standard Deviation 4.1 |
| NIOV - Oxygen | Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions | 17.5 minutes | Standard Deviation 5.7 |
| Nasal Cannula Oxygen | Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions | 11.4 minutes | Standard Deviation 6.8 |
| No Treatment | Exercise Duration for Constant Work Rate Exercise Tests Under 4 Test Conditions | 5.6 minutes | Standard Deviation 1.9 |
Comparison: The primary endpoint was difference in endurance between nasal cannula oxygen and NIOV+O2. Assuming 153 sec clinically important difference, 183 sec SD, and α=0.05, a sample size of 15 yielded 85% power.p-value: <0.05ANOVA
p-value: <0.05ANOVA
p-value: <0.05ANOVA
Secondary
Borg Dyspnea Score During Constant Workrate Exercise at Isotime
Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control) at isotime. Borg Dyspnea Score ranges in values from 0 to 10. The lower score represent better outcome. 0 = No breathlessness at all, representing better outcome 10 = Maximum breathlessness, representing worse outcome
Time frame: Outcome was measured in each Study day 1,2,3 and 4. Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxygen and N
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIOV - Room Air | Borg Dyspnea Score During Constant Workrate Exercise at Isotime | 3.3 units on a scale | Standard Deviation 1.8 |
| NIOV - Oxygen | Borg Dyspnea Score During Constant Workrate Exercise at Isotime | 1.8 units on a scale | Standard Deviation 1.3 |
| Nasal Cannula Oxygen | Borg Dyspnea Score During Constant Workrate Exercise at Isotime | 2.5 units on a scale | Standard Deviation 1.7 |
| No Treatment | Borg Dyspnea Score During Constant Workrate Exercise at Isotime | 4.6 units on a scale | Standard Deviation 2 |
Comparison: Per protocolp-value: <0.05ANOVA
p-value: <0.05ANOVA
p-value: <0.05ANOVA
Secondary
SpO2 During Constant Workrate Exercise at Isotime
Mean differences between NIOV - oxygen, NIOV - Room Air, Nasal Cannula Oxygen, and no treatment (control).
Time frame: Outcome was measured in each of the Study day 1,2, 3 and 4. Study days 1,2,3, and 4; Day 1 for no treatment; day 2 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 3 for no treatment and NIOV - Room Air and NIOV - oxygen; Day 4 for NIOV - oxyg
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIOV - Room Air | SpO2 During Constant Workrate Exercise at Isotime | 87.9 percentage of oxyHb saturation | Standard Deviation 3.8 |
| NIOV - Oxygen | SpO2 During Constant Workrate Exercise at Isotime | 98.5 percentage of oxyHb saturation | Standard Deviation 1 |
| Nasal Cannula Oxygen | SpO2 During Constant Workrate Exercise at Isotime | 92.7 percentage of oxyHb saturation | Standard Deviation 3.9 |
| No Treatment | SpO2 During Constant Workrate Exercise at Isotime | 88.2 percentage of oxyHb saturation | Standard Deviation 2.2 |
Comparison: One-way, repeated-measures ANOVA and Newman-Keuls multiple comparisons testp-value: <0.05ANOVA
p-value: <0.05ANOVA
p-value: <0.05ANOVA