Emphysema
Conditions
Keywords
emphysema, endobronchial valve, treatments, pulmonary rehabilitation, lung volume reduction
Brief summary
The purpose of this research is to study an investigational medical device that is designed to produce lung volume reduction in diseased areas of the lungs in patients with severe emphysema.
Detailed description
The Pulmonx Zephyr Endobronchial Valve (EBV) is an implantable bronchial valve intended to decrease volume in targeted regions of the lung. It is indicated for the treatment of patients with severe emphysema. The EBV are placed in the diseased region of the lung using bronchoscopy. Bronchoscopy is a way to access the lungs using a small tube with a camera on the end. As the diseased region of the lung shrinks in size, healthier regions may expand and function more efficiently, resulting in improved breathing. The LIBERATE Study is a clinical trial with two groups. Participants are assigned at random to the 'Treatment' group or to the 'Control' group. The 'Treatment' group will receive the Zephyr Endobronchial Valve (EBV) in combination with optimal medical therapy. The 'Control' group will receive optimal medical therapy alone. For every three participants in the study, two will go into the 'Treatment' group and one will go into the 'Control' group. It is hypothesized that after placement of the EBV, lung function will be improved as compared to standard medical therapy alone. Based on the 12-month follow up data from the LIBERATE Study, the Zephyr Endobronchial Valve System was approved by the FDA for the treatment of severe emphysema in June 2018. Following this PMA approval, and in agreement with the FDA, the ongoing long term follow-up (out to 5 years) of patients in the LIBERATE Study will now be conducted as a Post-approval study under the auspices of the LIBERATE Extension Study. This is an administrative change with absolutely no change to the design or conduct of the study and, therefore has no material impact to the study participants or the study sites. All annual follow-up visits and evaluations are per the original LIBERATE Study protocol. Reporting to the FDA will be as the LIBERATE Extension Study.
Interventions
DEVICEEBV
This study arm will undergo EBV treatment and also receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.
This study arm will receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.
Sponsors
Pulmonx Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Clinical and radiological evidence of emphysema * Nonsmoking for 4 months prior to screening interview * BMI less than 35 kg/m2 * Stable on current medication regimen * Forced expiratory volume in one second (FEV1) between 15% and 45% of predicted value * Residual Volume less than 175% predicted (determined by body plethysmography) * Little or no collateral ventilation (CV-) as determined using the Chartis System
Exclusion criteria
* Had two or more hospitalizations over the last year for a COPD exacerbation * Had two or more hospitalizations over the last year for pneumonia * Had a prior lung transplant, lung volume reduction surgery, bullectomy or lobectomy * Had a heart attack or congestive heart failure within the last 6 months * Have heart arrhythmia * Is alpha-1 antitrypsin deficient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1-second (FEV1) | 1 year | The percentage of study participants in the Zephyr Valve EBV (Endobronchial Valves) treatment arm meeting the clinically significant threshold of \>15% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 1 year post-procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Post-bronchodilator Absolute Change | 1 year | Difference between study arms in absolute change from baseline for post-bronchodilator FEV1 score at 1 year (value at 1 year minus value at baseline). |
| St. George's Respiratory Questionnaire (SGRQ) | 1 year | Difference between study arms in 'absolute change from baseline' for SGRQ score at 1 year (value at 1 year minus value at baseline). The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts: Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease) A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations. |
| 6-minute Walk Distance | 1 year | Difference between study arms in 'absolute and percentage change from baseline' for 6MWD at 1 year (value at 1 year minus value at baseline). |
Countries
Brazil, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zephyr Valve Treatment and Optimal Medical Management This study arm will undergo The Zephyr Valve treatment along with optimal medical management, including smoking cessation program, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.
EBV: This study arm will undergo Zephyr Valve treatment and also receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary. | 128 |
| Optimal Medical Management This study arm will receive maximal medical management, including smoking cessation program support if necessary, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary.
Optimal Medical Management: This study arm will receive optimal medical management, including smoking cessation program support, pulmonary rehabilitation, usual medications and oxygen supplementation as necessary. | 62 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 1 |
| Overall Study | Excluded for medical reasons | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Zephyr Valve Treatment and Optimal Medical Management | Optimal Medical Management | Total |
|---|---|---|---|
| 6 Minute Walk Distance (m) | 311.3 meters STANDARD_DEVIATION 81.3 | 301.9 meters STANDARD_DEVIATION 78.5 | 308.3 meters STANDARD_DEVIATION 80.3 |
| Age, Continuous | 64 years STANDARD_DEVIATION 6.9 | 62.5 years STANDARD_DEVIATION 7.1 | 63.5 years STANDARD_DEVIATION 7 |
| BMI | 24.7 kg/m2 STANDARD_DEVIATION 3.9 | 24.3 kg/m2 STANDARD_DEVIATION 4.4 | 24.6 kg/m2 STANDARD_DEVIATION 4.1 |
| BODE Index | 5.3 Index STANDARD_DEVIATION 1.5 | 5.3 Index STANDARD_DEVIATION 1.6 | 5.3 Index STANDARD_DEVIATION 1.5 |
| Diffusing Capacity (mL CO/min/mm Hg) | 8.5 mL CO / min / mmHg STANDARD_DEVIATION 3.5 | 8.3 mL CO / min / mmHg STANDARD_DEVIATION 2.7 | 8.5 mL CO / min / mmHg STANDARD_DEVIATION 3.2 |
| Diffusing Capacity (% predicted) | 34.6 %predicted STANDARD_DEVIATION 11.3 | 33.1 %predicted STANDARD_DEVIATION 9.8 | 34.1 %predicted STANDARD_DEVIATION 10.9 |
| FEV1 Post-Bronchodilator (liters) | 0.8 liters STANDARD_DEVIATION 0.3 | 0.8 liters STANDARD_DEVIATION 0.2 | 0.8 liters STANDARD_DEVIATION 0.2 |
| FEV1 Post-Bronchodilator (% predicted) | 28.0 %predicted STANDARD_DEVIATION 7.5 | 26.2 %predicted STANDARD_DEVIATION 6.3 | 27.4 %predicted STANDARD_DEVIATION 7.1 |
| FVC (liters) | 2.6 liters STANDARD_DEVIATION 0.9 | 2.6 liters STANDARD_DEVIATION 0.8 | 2.6 liters STANDARD_DEVIATION 0.8 |
| FVC (% predicted) | 71.2 %predicted STANDARD_DEVIATION 16 | 68.5 %predicted STANDARD_DEVIATION 13.6 | 70.3 %predicted STANDARD_DEVIATION 15.3 |
| GOLD Stage GOLD Stage III | 54 Participants | 16 Participants | 70 Participants |
| GOLD Stage GOLD Stage IV | 74 Participants | 46 Participants | 120 Participants |
| Height | 65.7 inches STANDARD_DEVIATION 4 | 66.3 inches STANDARD_DEVIATION 3.4 | 65.9 inches STANDARD_DEVIATION 3.9 |
| mMRC Dyspnea Grade score | 2.4 score STANDARD_DEVIATION 1 | 2.2 score STANDARD_DEVIATION 0.8 | 2.4 score STANDARD_DEVIATION 0.9 |
| Pack Years Smoking History | 50.8 pack-years STANDARD_DEVIATION 26.9 | 48.6 pack-years STANDARD_DEVIATION 28.5 | 50.1 pack-years STANDARD_DEVIATION 27.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 117 Participants | 57 Participants | 174 Participants |
| Region of Enrollment Brazil | 13 participants | 6 participants | 19 participants |
| Region of Enrollment Netherlands | 17 participants | 8 participants | 25 participants |
| Region of Enrollment United Kingdom | 10 participants | 6 participants | 16 participants |
| Region of Enrollment United States | 88 participants | 42 participants | 130 participants |
| Residual Volume (% predicted) | 224.5 %predicted STANDARD_DEVIATION 42.5 | 224.6 %predicted STANDARD_DEVIATION 38.9 | 224.5 %predicted STANDARD_DEVIATION 41.2 |
| Residual Volume (RV) (liters) | 4.7 liters STANDARD_DEVIATION 1.1 | 4.8 liters STANDARD_DEVIATION 0.9 | 4.7 liters STANDARD_DEVIATION 1 |
| Sex: Female, Male Female | 72 Participants | 29 Participants | 101 Participants |
| Sex: Female, Male Male | 56 Participants | 33 Participants | 89 Participants |
| SGRQ Total score | 55.2 score on a scale STANDARD_DEVIATION 14.1 | 53.1 score on a scale STANDARD_DEVIATION 14.1 | 54.5 score on a scale STANDARD_DEVIATION 14.1 |
| Total Lung Capacity (% predicted) | 133.5 %predicted STANDARD_DEVIATION 21.2 | 130.2 %predicted STANDARD_DEVIATION 12.4 | 132.4 %predicted STANDARD_DEVIATION 18.8 |
| Total Lung Capacity (TLC) (liters) | 7.5 liters STANDARD_DEVIATION 1.6 | 7.6 liters STANDARD_DEVIATION 1.4 | 7.6 liters STANDARD_DEVIATION 1.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 128 | 1 / 62 |
| other Total, other adverse events | 124 / 128 | 46 / 62 |
| serious Total, serious adverse events | 77 / 128 | 24 / 62 |
Outcome results
Primary
Forced Expiratory Volume in 1-second (FEV1)
The percentage of study participants in the Zephyr Valve EBV (Endobronchial Valves) treatment arm meeting the clinically significant threshold of \>15% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 1 year post-procedure.
Time frame: 1 year
Population: Intent-to-Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zephyr Valve Treatment and Optimal Medical Management | Forced Expiratory Volume in 1-second (FEV1) | 61 Participants |
| Optimal Medical Management | Forced Expiratory Volume in 1-second (FEV1) | 10 Participants |
Secondary
6-minute Walk Distance
Difference between study arms in 'absolute and percentage change from baseline' for 6MWD at 1 year (value at 1 year minus value at baseline).
Time frame: 1 year
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zephyr Valve Treatment and Optimal Medical Management | 6-minute Walk Distance | 13.0 meters | Standard Deviation 81.5 |
| Optimal Medical Management | 6-minute Walk Distance | -26.3 meters | Standard Deviation 81.5 |
Secondary
FEV1 Post-bronchodilator Absolute Change
Difference between study arms in absolute change from baseline for post-bronchodilator FEV1 score at 1 year (value at 1 year minus value at baseline).
Time frame: 1 year
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zephyr Valve Treatment and Optimal Medical Management | FEV1 Post-bronchodilator Absolute Change | 0.1 liters | Standard Deviation 0.2 |
| Optimal Medical Management | FEV1 Post-bronchodilator Absolute Change | -0.003 liters | Standard Deviation 0.2 |
Secondary
St. George's Respiratory Questionnaire (SGRQ)
Difference between study arms in 'absolute change from baseline' for SGRQ score at 1 year (value at 1 year minus value at baseline). The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts: Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease) A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: 1 year
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zephyr Valve Treatment and Optimal Medical Management | St. George's Respiratory Questionnaire (SGRQ) | -7.6 score on a scale | Standard Deviation 15.7 |
| Optimal Medical Management | St. George's Respiratory Questionnaire (SGRQ) | -0.5 score on a scale | Standard Deviation 15.5 |