COPD, COPD (Chronic Obstructive Pulmonary Disease), Emphysema, Emphysema or COPD, Emphysema, Pulmonary
Conditions
Keywords
Lung Volume Reduction, bronchoscopic lung volume reduction, ETLA, BTVA, LVR, Lung Disease, obstructive, Chronic Obstructive Lung Disease, Respiratory Tract Disease
Brief summary
The goal of this clinical trial is to learn if bronchoscopic lung volume reduction with endobronchial thermal liquid ablation (ETLA) works to treat severe emphysema in terms of feasibility and safety. Participants will: * Have up to two ETLA procedures * Complete five clinic follow-up visits and two virtual follow-up visits.
Detailed description
ETLA offers the potential to result in significant lung volume reduction of hyperinflated emphysematous regions, providing clinically meaningful improvement in pulmonary function and quality of life to a broad population of patients with severe emphysema. The REDUCE EU Pilot study will primarily evaluate the feasibility and safety of ETLA treatment in patients with severe emphysema. Secondarily, the study will evaluate the efficacy of sequential ETLA treatment.
Interventions
DEVICEEndobronchial Therman Liquid Ablation (ETLA)
The ETLA System is a minimally invasive bronchoscopic treatment designed to deliver heated normal saline to targeted emphysematous lung regions with hyperinflation to cause tissue ablation and subsequent volume reduction as a means for treating emphysema. The ETLA procedures will be performed under general anesthesia. Each procedure will be limited to treatment in a single lung, with either unilateral or bilateral treatment over the two procedures.
Sponsors
Morair Medtech, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is prospective, single-arm and multi-center.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 40 years old * Diagnosis of COPD with FEV1/FVC less than 0.7 post-bronchodilation * Post-bronchodilator Forced Expiratory Volume (FEV1) ≥ 20% and ≤ 49% of predicted value * Total lung capacity (TLC) ≥ 100% predicted * Residual volume (RV) ≥ 175% predicted * 6 Minute Walk Distance (6MWD) ≥ 140 meters * Dyspnea scoring ≥ 1 on the modified Medical Research Council scale (mMRC) * Blood gas values of PCO2 ≤ 55 mmHg; PO2 ≥ 45 mmHg on room air * Optimized medical management (consistent with GOLD guidelines) as confirmed by the Investigator * Non-smoking for 3 months prior to study enrollment, as confirmed by lab testing * Participant must engages in physical exercise beyond activities of daily living (i.e., a walking program, pulmonary rehabilitation) on n a regular basis for more than 6 weeks prior to enrollment and agree to continue the activity throughout study participation * Participant must live within approximately 1 hour of the study hospital, or live within 1 hour of adequate regional care, or be willing to remain in the hospital for at least five days post-procedure * Vaccinated for COVID-19, pneumococcus, and influenza (per European Union and Member State guidelines) or documented clinical intolerance or documented patient refusal * Cognitively able to provide written informed consent and willing to comply with study requirements * Severe emphysematous lung subsegments eligible for ETLA treatment
Exclusion criteria
* Body mass index (BMI) \< 16 kg/m\^2 or ≥ 33 kg/m\^2 * DLCO \< 20% predicted * Chronic bronchitis as defined by cough and sputum production for at least 3 months per year for two consecutive years, in the absence of other conditions that can explain these symptoms * 75ml or greater sputum production per day most days of the week * Greater than two hospitalizations for COPD exacerbations and/or pneumonia in the 12 months prior to enrollment * Diagnosis of asthma that is confirmed according to the Global Initiative for Asthma (GINA) guidelines * Prior lung volume reduction via endobronchial valves(s), coil(s), vapor and/or polymer. Patients whose valves have been removed \> 3 months previously can be treated if a baseline bronchoscopy reveals no airway obstruction or obvious tissue granulation and the reason for valve removal was not for complications e.g., Pneumonia, severe exacerbation, or pneumothorax. * Pulmonary hypertension * Alpha-1 antitrypsin deficiency * Uncontrolled diabetes mellitus * Prior heart or lung transplant * Myocardial infarction or stroke within the 12 months of enrollment * Diagnosis of heart failure * Heart failure requiring hospitalization, within 6 months prior to enrollment * History of bleeding disorders or enhanced predisposition to bleeding * History of severe/massive hemoptysis defined as \>200ml of blood loss in \< 24 hours * Unable to discontinue anti-coagulants or platelet inhibitors (acetylsalicylic acid \[ASA\]and non-ASA, including low dose) for at least 7 days prior to each procedure (or as per physician discretion based on the specific agent) and for at least 6 weeks after each procedure * Daily systemic steroids equivalent to \> 15mg prednisolone * Immunosuppressive drugs, such as for the treatment of cancer, autoimmune disease, or prevention of tissue/organ rejection * Pregnant, lactating, or women of childbearing potential that plan to become pregnant within the study duration * Currently enrolled in another trial studying an experimental treatment * Any disease or condition likely to limit survival to less than one year * Concomitant illnesses or medications that may pose a significant increased risk for complications following treatment with ETLA * Any condition that would interfere with evaluation or completion of the study including study assessments and procedures, including bronchoscopy. * Active aspergillus infection * Clinically significant bronchiectasis as determined by the Investigator * Radiological evidence of bronchiectasis in target region(s) and/or cystic radiological bronchiectasis in any region of the lungs * Clinically significant pulmonary fibrosis * Lung nodule not proven stable unless proven to have benign pathology * Large bulla (defined as \> 1/3 volume of a lung) * Prior Lung Volume Reduction Surgery (LVRS), bullectomy, or lobectomy * The remaining lung tissue NOT targeted for ETLA treatment is too highly diseased * Active respiratory infection or recent respiratory infection with resolution \< 4 weeks prior to screening or procedure * Recent COPD exacerbation within \< 6 weeks prior to screening or procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of procedures where the device operated as intended | Through completion of the second procedure, approximately 13 weeks | Percent of procedures where the device operated as intended per the Instructions for Use (IFU) |
| Incidence of serious adverse events (SAE) | 6 months | Incidence of serious adverse events (SAE) associated with the ETLA device and/or procedure as adjudicated by an independent medical monitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual volume (RV) change | 3, 6, and 9 months | Change in residual volume (RV) (mL, % change in absolute and % predicted) |
| FEV1 change | 3, 6, and 9 months | Change in Forced Expiratory Volume in the first second (FEV1) (mL, % change in absolute and % predicted) |
| Incidence of adverse events | 9 months | Incidence of all adverse events associated with the ETLA device and/or procedure |
| 6MWT change | 3, 6, and 9 months | Change in Six Minute Walk Test (6MWT) |
| SGRQ-C change | 3, 6, and 9 months | Change in SGRQ-C (Saint George Respiratory Questionnaire-COPD) |
| RV/TLC change | 3, 6, and 9 months | Change in residual volume (RV) over total lung capacity (TLC) (RV/TLC) |
| Incidence of serious adverse events (SAE) | 9 months | Incidence of serious adverse events (SAE) associated with the ETLA device and/or procedure as adjudicated by an independent medical monitor |
Other
| Measure | Time frame | Description |
|---|---|---|
| DLCO change | 3, 6, and 9 months | Change in DLCO (lung diffusion test) |
| Target Lobe Volume Reduction | Baseline to 3 months post-procedure 1, 3 months post-procedure 1 to 3 months post-procedure 2 | Target Lobe Volume Reduction (TLVR) as measured by CT scan quantified by the reduction in the volume of the targeted lobe(s) (reported in mL) |
| mMRC change | 3, 6, and 9 months | Change in mMRC (Modified Medical Research Council dyspnea questionnaire) |
| Cumulative Lobar Volume Reduction | Through follow-up of the second procedure, approximately 6 Months | Cumulative Lobar Volume Reduction as measured by CT scan, quantified by the summation of TLVR through both procedures (reported in mL) |
| Catheter positioning allowing treatment | Through completion of the second procedure, approximately 13 weeks | Percent of target regions where the catheter is placed in the target airway with positioning allowing treatment |
| Heated saline at predetermined volume | Through completion of the second procedure, approximately 13 weeks | Percent of target regions where heated saline is delivered at the predetermined volume per treatment plan |
| Auxiliary reduction | Through follow-up of the second procedure, approximately 6 Months | Number of procedures where auxiliary reduction is observed in a region not predicted |
| Responder analyses | 3, 6, and 9 months | Responder analyses for: * Improvement in FEV1 of ≥ 12% * Reduction in RV of ≥ 6% * Reduction in RV/TLC of ≥ 3% * Increase in 6MWD of ≥ 26 meters * Improvement in SGRQ-C of ≥ 4 points |
| TLC change | 3, 6, and 9 months | Change in Total Lung Capacity (TLC) |
| CAT score change | 3, 6, and 9 months | Change in COPD Assessment Test (CAT) score |
| BODE index change | 3, 6, and 9 months | Change in BODE index (body-mass index, airflow obstruction, dyspnea, and exercise) |
Countries
Austria, Germany, Netherlands
Outcome results
None listed