Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000679482
Ethics application status
Approved
Date submitted
29/05/2025
Date registered
26/06/2025
Date last updated
26/06/2025
Date data sharing statement initially provided
26/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
REDUCE Optimization Study - A Study of Endobronchial Thermal Liquid Ablation (ETLA) for the Treatment of Severe Emphysema (CSP-12225)
Scientific title
The REDUCE Optimization Study – A Study of Endobronchial Thermal Liquid Ablation (ETLA) for the Treatment of Severe Emphysema in participants with Chronic Obstructive Pulmonary Disease (csp-12225)
Secondary ID [1] 314521 0
csp-12225
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12622001327774 - the first in human trial for the ETLA system in patients with severe COPD. This trial is intended to optimize the ETLA treatment first investigated in the study referenced.

Health condition
Health condition(s) or problem(s) studied:
Severe emphysema (Gold 3 or 4) 337610 0
Condition category
Condition code
Respiratory 333950 333950 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 provides 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 Optimization 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.
Each procedure will target 5-15% of a participant's total lung volume. These volumes are based on volumetric CT analysis. The dose of saline delivered to the lungs will also be adjusted relative to a target ratio of saline to amount of lung region to be treated. Enrollment of the study will be conducted in two phases with the second half of the study, the last 15 of 30 participants, being treated with a slightly higher dose range (higher saline volume to target lung tissue). It is anticipated that the higher dose ratio will result in more complete lung volume reduction at a sub-segmental level and larger improvement in lung function.
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.
Intervention code [1] 331151 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341632 0
Efficacy: Change in residual lung volume (mL, % change in absolute and % predicted) from baseline
Timepoint [1] 341632 0
6 months following ETLA procedure 2.
Primary outcome [2] 341633 0
Efficacy: Change in forced expiratory volume (FEV1; mL, % change in absolute and % predicted) from baseline
Timepoint [2] 341633 0
6 months following ETLA procedure 2.
Secondary outcome [1] 448138 0
Safety: Incidence of all adverse events associated with the ETLA device and/or procedure through 9 months post-procedure 1
Timepoint [1] 448138 0
Collectively at the end of 9 months post ETLA procedure 1.
Secondary outcome [2] 448139 0
Safety: Incidence of serious adverse events (SAE) associated with the ETLA device and/or procedure through 9 months post-procedure 1 as adjudicated by an independent medical monitor.
Timepoint [2] 448139 0
Collectively at the end of 9 months post ETLA procedure 1
Secondary outcome [3] 448140 0
Efficacy: Change in residual volume relative to total lung volume from baseline (RV/TLC) as a composite endpoint.
Timepoint [3] 448140 0
3 months following ETLA procedure 1 and 2 and 6 months following ETLA procedure 2
Secondary outcome [4] 448141 0
Efficacy: Change in 6 minute walk test distance from baseline
Timepoint [4] 448141 0
3 months following ETLA procedure 1 and 2 and 6 months following ETLA procedure 2
Secondary outcome [5] 448142 0
Efficacy: Change in St. George's Respiratory Questionnaire score from baseline
Timepoint [5] 448142 0
3 months following ETLA procedure 1 and 2 and 6 months following ETLA procedure 2

Eligibility
Key inclusion criteria
1. Age greater than or equal to 40 years old
2. Diagnosis of COPD with FEV1/FVC less than 0.7 post-bronchodilation
3. Post-bronchodilator FEV1 greater than or equal to 20% and less than or equal to 49% of predicted value
4. Total lung capacity TLC greater than or equal to 100% predicted
5. Residual volume (RV) greater than or equal to 175% predicted
6. 6MWD greater than or equal to 140 meters
7. Dyspnea scoring greater than or equal to 1 on the modified Medical Research Council scale (mMRC)
8. PaCO2 less than or equal to 55 mmHg; PaO2 greater than or equal to 45 mmHg on room air
9. Optimized medical management (consistent with GOLD guidelines) as confirmed by the Investigator
10. Non-smoking for 3 months prior to study enrollment, as confirmed by:
• Negative cotinine urine analysis or serum cotinine level of less than or equal to 10 ng/ml, OR
• Negative carboxyhemoglobin (COHb) test (less than or equal to 2.5%)
11. The patient engages in physical exercise beyond activities of daily living (i.e., a walking program, pulmonary rehabilitation)
• On a regular basis for more than 6 weeks, AND
• Is continuing the activity at enrollment, AND
• Agrees to continue the activity throughout study participation
12. Patient must meet ONE of the following criteria for distance from treating hospital:
• Live within approximately 1 hour of the study hospital, OR
• If > 1 hour from study hospital, patient lives within approximately 1 hour of regional care that is sufficient to handle an emergency pulmonary event in COPD patients or must be willing to remain in the hospital for at least 5 days post-procedure or stay at local accommodation for at least 5 days post-procedure
13. Vaccinated per general health recommendations during the global pandemic as well as pneumococcus and influenza (per Australian Government and State guidelines) or documented clinical intolerance or documented patient refusal
14. Cognitively able to provide written informed consent and willing to comply with study requirements
15. Severe emphysematous subsegments eligible for ETLA treatment
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Body mass index (BMI) < 16 kg/m2 or less than or equal to 33 kg/m2
2. DLCO < 20% predicted
3. 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
4. 75ml or greater sputum production per day most days of the week
5. Greater than two hospitalizations for COPD exacerbations and/or pneumonia in the 12 months prior to enrollment
6. Diagnosis of asthma that is confirmed according to the Global Initiative for Asthma (GINA) guidelines
7. 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.
8. Pulmonary hypertension:
• History of cor pulmonale, OR
• mPAP >20mm Hg in the 12 months prior to enrollment, OR
• RV estimated systolic pressure >45 mmHg in the 12 months prior to enrollment
9. Alpha-1 antitrypsin deficiency
10. Uncontrolled diabetes mellitus with an HbA1c >9.0% within 6 months of enrollment
11. Prior heart or lung transplant
12. Myocardial infarction or stroke within the 12 months of enrollment
13. Diagnosis of heart failure: Left Ventricular Ejection Fraction (LVEF) less than or equal to 40% within 12 months prior to enrollment
14. Heart failure requiring hospitalization, within 6 months prior to enrollment
15. History of bleeding disorders or enhanced predisposition to bleeding
16. History of severe/massive hemoptysis defined as >200ml of blood loss in < 24 hours
17. Unable to discontinue anti-coagulants or platelet inhibitors (acetylsalicylic acid [ASA] >100mg and non-ASA) 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
18. Daily systemic steroids equivalent to > 15mg prednisone
19. Immunosuppressive drugs, such as for the treatment of cancer, autoimmune disease, or prevention of tissue/organ rejection
20. Pregnant, lactating, or women of childbearing potential that plan to become pregnant within the study duration
21. Currently enrolled in another trial studying an experimental treatment
22. Any disease or condition likely to limit survival to less than one year
23. Concomitant illnesses or medications that may pose a significant increased risk for complications following treatment with ETLA
24. Any condition that would interfere with evaluation or completion of the study including assessments and procedures, including bronchoscopy
25. Patients who qualify for endobronchial valves who have not been offered endobronchial valve therapy prior to inclusion in the REDUCE Optimization Study
26. Active aspergillus infection, including chronic aspergillus infection, aspergilloma, invasive aspergillosis, cavitation and/or history of aspergillus cavitation(s) or colonization confirmed by bronchoscopic culture*
27. Clinically significant bronchiectasis as determined by the Investigator
28. Radiological evidence of bronchiectasis in target region(s) and/or cystic radiological bronchiectasis in any region of the lungs*
29. Clinically significant pulmonary fibrosis*
30. Lung nodule not proven stable unless proven to have benign pathology*
31. Large bulla (defined as > 1/3 volume of a lung)*
32. Prior Lung Volume Reduction Surgery (LVRS), bullectomy, or lobectomy*
33. Contralateral lung tissue is too highly diseased, defined as %-950 = 50%, after both ETLA procedure treatment plans are finalized, as confirmed by QCT analysis
34. Active respiratory infection or recent respiratory infection with resolution < 4 weeks prior to screening or procedure
35. Recent COPD exacerbation within < 6 weeks prior to screening or procedure

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/07/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC

Funding & Sponsors
Funding source category [1] 319071 0
Commercial sector/Industry
Name [1] 319071 0
Morair Medtech LLC
Country [1] 319071 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Morair Medtech LLC
Address
Country
United States of America
Secondary sponsor category [1] 321531 0
Commercial sector/Industry
Name [1] 321531 0
Morair Medtech Pty Ltd
Address [1] 321531 0
Country [1] 321531 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317670 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 317670 0
Ethics committee country [1] 317670 0
Australia
Date submitted for ethics approval [1] 317670 0
26/03/2025
Approval date [1] 317670 0
30/04/2025
Ethics approval number [1] 317670 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 141758 0
Prof Daniel Steinfort
Address 141758 0
The Royal Melbourne Hospital, 300 Grattan Street Parkville, Victoria 3052
Country 141758 0
Australia
Phone 141758 0
+61 0416275750
Fax 141758 0
Email 141758 0
[email protected]
Contact person for public queries
Name 141759 0
Margaret Wierman
Address 141759 0
Morair Medtech 401 N 36th St. Seattle WA 98103
Country 141759 0
United States of America
Phone 141759 0
+18669653044
Fax 141759 0
Email 141759 0
[email protected]
Contact person for scientific queries
Name 141760 0
Margaret Wierman
Address 141760 0
Morair Medtech 401 N 36th St. Seattle WA 98103
Country 141760 0
United States of America
Phone 141760 0
+18669653044
Fax 141760 0
Email 141760 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Individual data sets will not be analyzed in this study.



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.