None listed
Conditions
Brief summary
This is a prospective, multi-center, single-arm phased study assessing the safety, feasibility and efficacy of the ETLA system for the treatment of severe emphysema with hyperinflation. 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 therapy will be delivered sequentially over two (2) procedures. The magnitude of clinical benefit associated with ETLA is anticipated to correlate with the relative volume of diseased tissue removed/reduced, therefore it is anticipated that higher relative volume treated may result in larger improvement.
Interventions
The Morair Medtech (Endobronchial Thermal Liquid Ablation) ETLA System is a medical device consisting of the ETLA catheter and generator and TRST (Treatment Regional Selection Tool). 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 REDUCE Study involves the completion of two separate proc
The Morair Medtech (Endobronchial Thermal Liquid Ablation) ETLA System is a medical device consisting of the ETLA catheter and generator and TRST (Treatment Regional Selection Tool). 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 REDUCE Study involves the completion of two separate procedures using the ETLA System scheduled approximately 3 months apart. The delivery of the second treatment will be dependent upon the health and wellbeing of the participant (assessed prior to the second procedure). Each patient will be monitored and assessed for safety events and treatment efficacy for 9 months after the first ETLA procedure. The follow-up assessments will include regular pulmonary function tests, laboratory blood draws, and quality of life assessments The procedures will be performed in a bronchoscopy suite by a suitably qualified interventional pulmonologist (respiratory physician). ETLA therapy involves the delivery of up to 50ml of heated normal saline (0.9% Normal Saline) at 95 degrees celcius to lung regions identified by the treating physician using the TRST. The TRST presents the treating physician with possible subsegments to be treated based on an analysis of an HRCT of the patient’s chest. These selections are used to produce a treatment plan, including the associated dose for each subsegment, based on the individual’s specific airway volumes and disease severity. Treatment over the two ETLA procedures may be unliateral or bilateral, however only one lung can be treated in each of the two ETLA procedures. The decision as to which lung regions to treat during each procedure will be based upon disease severity and volume of lung segments and is ultimately up to the interventional pulmonologist. Subjects will be anaesthetised and paralysed for the procedure. Exact drugs and dosages of anaesthetic agents utlised will be decided on a patient by patient basis after assessment by a suitably qualified anaesthetist. The target lesions to undergo ETLA will be decided upon by the interventional pulmonologist based upon data obtained from analysis of High Resolution CT Scan (HRCT) of the chest of potential subjects. Following the decision of the interventional pulmonologist a treatment plan will be provided by Morair Medtech. The ETLA procedure is expected to take approximately 1 hour from the time of the participant being placed on the operating table to the time of being removed from the table. As mentioned above the procedure will be performed in an operating theatre or interventional bronchoscopy suite. The safety and efficacy of the ETLA procedures will be monitored by a series of scheduled CT Scans throughout the 9 month follow-up period. Enrollment will be completed in a phased approach, with each phase defined by a prespecified target procedure volume (TPV) range, where TPV is the total relative (%) volume of all treated regions in a single procedure. The study will assess ETLA at two (2) Targeted Procedure Volume (TPV) ranges. The TPV range provides the minimum and maximum treatment volume as a percentage of the relative volume of the total lung volume (both lungs) for each patient to be targeted within a given phase of the study. This volume will be estimated based on volumetric CT analysis. The magnitude of clinical benefit associated with ETLA is anticipated to correlate with the relative volume of diseased tissue removed/reduced, therefore it is anticipated that higher relative volume treated may result in larger improvement. Two (2) TPV ranges have been identified for the study based on preclinical animal to human lung volume translation, as follows: Phase 1: >5% to < 10% of total lung volume (both lungs) treated per procedure Phase 2: > than 10% to < 15% of total lung volume (both lungs) treated per procedure This study will begin in phase 1, which consists of treating within the minimum TPV percentage anticipated to give the patient a reasonable opportunity for clinical benefit, while keeping safety as the primary consideration. The TPV range will not be changed (increased or decreased) prior to conducting a comprehensive phase review with the Data Safety Monitoring Board (DSMB). The phase review includes three (3) month follow-up safety and efficacy data, including imaging analysis, on a minimum of five (5) ETLA procedures. The outcome of the phase review will determine if enrollment should continue at a given TPV range to collect additional data or if the DSMB determines that the data supports a change to Phase 2. Subjects enrolled with their first procedure in Phase 1 may be treated with their second procedure in Phase 2 of the study dependent upon their overall enrolment position in the cohort.
Sponsors
Morair Medtech LLC
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria 1. Age greater than or equal to 18 and less than or equal to 75years old 2. Post-bronchodilator FEV1 greater than or equal to 20% and less than or equal to 50% of predicted value 3. Post-bronchodilator total lung capacity TLC greater than or equal to 100% predicted 4. Post-bronchodilator residual volume (RV) greater than or equal to 175% predicted 5. 6MWD (Six Minute Walk Distance) greater than or equal to 150 meters 6. PaCO2 less than or equal to 50 mm Hg and PaO2 greater than 45 mm Hg on room air 7. Non-smoking for 3 months prior to study enrollment, as confirmed by; • Negative urine analysis or serum cotinine level of less than or equal to 10 ng/mL, or if using smoking cessation product(s) containing nicotine at screening, serum cotinine level less than or equal to 13.7 ng/ml OR • Negative carboxyhemoglobin (COHb) test (less than or equal to 2.5%) 8. Optimized medical management (consistent with GOLD guidelines) 9. Evidence of completed pulmonary rehabilitation: • greater than or equal to 6 weeks out-patient or greater than or equal to 3 weeks in-patient within 6 months of enrollment; OR • Patient has or continues to participate in regular physical activity beyond activities of daily living (e.g., a walking program) for greater than 6 weeks under the supervision / in the opinion of a health care professional within 6 months of enrollment 10. Patient must meet ONE of the following criteria for distance from treating hospital: • Lives within approximately 1 hour of the study hospital • If greater than 1 hour from study hospital, lives within approximately 1 hour of regional care is sufficient to handle an emergency pulmonary event in COPD patients with surgical suite • If greater than 1 hour from study hospital and there is not sufficient regional care, patient is willing to stay at local hotel or other accommodation through 5-days post-discharge 11.See Public Notes at end of form 12. Current pneumococcus and influenza vaccination (or documented clinical intolerance or documented patient refusal) 13. Cognitively and physically able to provide written informed consent Radiological Inclusion Criteria 14. Severe emphysematous sub-segments eligible for ETLA treatment where the volume of targeted sub-segments must meet the minimum phase volume, with the total targeted volume allowing for two (2) ETLA procedures. Eligible sub-segments are defined as having greater than or equal to 25% destruction %-950 HU per Quantitative CT analysis with a heterogeneity index (HI) greater than 1.2. Note: Chest CT analysis by QCT Core lab
Exclusion criteria
General Exclusion Criteria 1. DLCO less than 20% predicted 2. Clinical evidence of Pulmonary hypertension (mPAP greater than 20mm Hg) or RV estimated systolic pressure greater than 45 mmHg as determined by recent (within the previous 12 months) echocardiogram or history of cor pulmonale 3. Clinically significant sputum production (greater than 5 tbsp per day) 4. Greater than two (2) COPD exacerbations or pneumonia episodes requiring hospitalization in the last year. 5. History of active asthma 6. Alpha-1 antitrypsin deficiency 7. Daily systemic steroids greater than 12.5 mg prednisolone (or equivalent). 8. Prior lung volume reduction via endobronchial valves(s), coil(s), vapor and/or polymer. Note: Patients whose valves have been removed greater than 3 months prior can be treated if baseline bronchoscopy reveals no airway obstruction or obvious tissue granulation and the reason for valve removal was not complications e.g., pneumonia, severe exacerbation, or pneumothorax. 9. Myocardial Infarction or heart failure exacerbation within 6 months of screening. 10. Diagnosis of systolic heart failure with LVEF less than 45% determined by recent echocardiogram (completed within 12 months prior to screening). Note: Subjects with no CHF diagnosis do NOT require current echo. 11. History of bleeding disorders or enhanced predisposition to bleeding. 12. Unable to discontinue anti-coagulants or platelet inhibitors (non-ASA and ASA greater than 100mg daily) pre-procedure and for greater than 6 weeks post-procedure. 13. Body mass index (BMI) greater than 30 kg/m2 or less than 16 kg/m2 14. Immunosuppressive drugs, such as for the treatment of cancer, autoimmune disease, or prevention of tissue/organ rejection. 15. Pregnant, lactating, or women of childbearing potential that plan to become pregnant within the study duration 16. Active aspergillus infection, history of aspergillus colonization or cavitation(s). 17. Lung nodule not proven stable unless proven to have benign pathology** 18. Prior lung transplant, bullectomy or lobectomy** 19. Any disease or condition likely to limit survival to less than one year 20. Concomitant illnesses or medications that may pose a significant increased risk for complications following treatment with ETLA. 21. Currently enrolled in another trial studying an experimental treatment. 22. Any condition in the opinion of the Investigator that would interfere with completion of the study including study assessments and procedure including bronchoscopy. Radiological Exclusion Criteria 23. Remaining lung tissue NOT targeted for ETLA treatment is too highly diseased, defined as %-950 HU greater than or equal to 50%, after both ETLA procedure treatment plans are finalized. Note: Applies to both lungs, each individually assessed, regardless of whether lung is targeted for ETLA (unilateral or bilateral treatment). Note: Chest CT analysis by QCT Core lab 24. Significant bronchiectasis* 25. Significant pulmonary fibrosis* 26. Large bulla (defined as greater than 1/3 volume of a lung)* 27. Paraseptal emphysema* 28. Radiology Eligibility Reviewer indicates patient is not ideal for the treatment* * Assessed by Radiology Eligibility Reviewer ** Assessed by Radiology Eligibility Reviewer in addition to site radiology Pre-procedural Exclusion Criteria 29. Evidence of active infection in the lungs at the time of procedure (ex: elevated temperature, increased WBC from baseline, purulent sputum, or other indication of infection as compared to baseline measurements). 30. Recent respiratory infection with resolution in preceding 4 weeks of procedure. 31. Recent COPD exacerbation with resolution in preceding 6 weeks of procedure.
Outcome results
None listed