Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001327774
Ethics application status
Approved
Date submitted
25/08/2022
Date registered
12/10/2022
Date last updated
3/04/2024
Date data sharing statement initially provided
12/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The REDUCE Study – Safety of the Endobronchial Thermal Liquid Ablation (ETLA) for the Treatment of Severe Emphysema with hyperinflation – A First in Human Study (CSP-11121
Scientific title
The REDUCE Study – Safety of the Endobronchial Thermal Liquid Ablation (ETLA) for the Treatment of Severe Emphysema with hyperinflation – A First in Human Study (CSP-11121)
Secondary ID [1] 307838 0
CSP-11121
Universal Trial Number (UTN)
Trial acronym
REDUCE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Emphysema 327445 0
Severe Emphysema (Gold Stage 3 or 4) 327446 0
Condition category
Condition code
Respiratory 324564 324564 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 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.
Intervention code [1] 324302 0
Treatment: Devices
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332390 0
Safety:
Incidence of serious adverse events (SAE) and Major Medical Complications (MMC)* associated with the ETLA device and/or procedure through 9 months post initial procedure as adjudicated by an independent medical monitor.
* Includes device and/or procedure related events requiring ICU admission, SAEs requiring additional procedure (Bronchoscopic or surgical) and death
Adverse events such as mild exacerbation of COPD will be determined primarily by clinical examination and if required the sourcing of de-identified medical records from healthcare providers or institutions.
Timepoint [1] 332390 0
At the end of 9 months post second ETLA treatment procedure.
Secondary outcome [1] 413307 0
Feasibility:
The following endpoint will be assessed for ETLA procedure 1
• The Morair ETLA System operated as intended per the (Instructions for Use) IFU
Timepoint [1] 413307 0
Assessed during ETLA procedure 1
Secondary outcome [2] 414383 0
Procedure: Ability to place catheter in target airways with positioning allowing treatment
Note: Target airways are identified in the patient Treatment Plan.
This outcome will be assessed by the operator (physician) during the procedure and documented in the procedure notes in the subject medical record.
Timepoint [2] 414383 0
Assessed during ETLA procedures 1 and 2
Secondary outcome [3] 414384 0
Treatment: Ability to deliver predetermined volume of heated 95 degrees celcius saline to target airways. This outcome will be assessed by device diagnostic analytics and also the sponsor technicians who attend cases to support the technology.
Timepoint [3] 414384 0
Assessed during ETLA procedures 1 and 2
Secondary outcome [4] 414385 0
Lung volume reduction (LVR) reported in mL and % as measured by CT scan through 3 months post-procedure
Note: LVR analysis completed by independent radiology Core lab.
Timepoint [4] 414385 0
Assessed at 3 months following ETLA procedures 1 and 2
Secondary outcome [5] 414386 0
Residual Volume change as measured by respiratory function tests (Spirometry) at 3 months post-procedure
Timepoint [5] 414386 0
Assessed at 3 months following ETLA procedures 1 and 2
Secondary outcome [6] 414494 0
Total Lung Capacity change as measured by respiratory function tests (Spirometry) at 3 months post-procedure
Timepoint [6] 414494 0
Assessed at 3 months following ETLA procedures 1 and 2
Secondary outcome [7] 414668 0
Feasibility:
The following endpoint will be assessed for ETLA procedure 2
• The Morair ETLA System operated as intended per the (Instructions for Use) IFU
Timepoint [7] 414668 0
Assessed during ETLA procedure 2

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size for this protocol is too small to permit a formal statistical analysis. Trends, particularly in reported adverse events, will be noted and characterized. A comprehensive listing, categorization, and assessment of causality will be provided for all serious and non-serious adverse events secondary to the ETLA procedure. Descriptive statistics will be used to summarize the secondary outcomes.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2022
Actual
17/11/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
30
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 23026 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 23027 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [3] 23029 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 38347 0
3050 - Parkville
Recruitment postcode(s) [2] 38348 0
2109 - Macquarie Park
Recruitment postcode(s) [3] 38350 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 312111 0
Commercial sector/Industry
Name [1] 312111 0
Morair Medtech LLC
Country [1] 312111 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Morair Medtech LLC
Address
401 N 36th St.
Suite 202
Seattle, WA 98103
Country
United States of America
Secondary sponsor category [1] 313633 0
Commercial sector/Industry
Name [1] 313633 0
Australian Healthcare Solutions Pty Ltd
Address [1] 313633 0
Level 1 424 Burke Road'
Camberwell, VIC 3124
Country [1] 313633 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311513 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 311513 0
Ethics committee country [1] 311513 0
Australia
Date submitted for ethics approval [1] 311513 0
26/04/2022
Approval date [1] 311513 0
14/07/2022
Ethics approval number [1] 311513 0
HREC/85966/MH-2022

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

Contacts
Principal investigator
Name 121362 0
Prof Alvin Ing
Address 121362 0
Macquarie University Hospital
3 Technology Place
Macquarie University, NSW 2109
Country 121362 0
Australia
Phone 121362 0
+61298123709
Fax 121362 0
Email 121362 0
[email protected]
Contact person for public queries
Name 121363 0
Margaret Wierman
Address 121363 0
Morair Medtech 401 N 36th St. Suite 202 Seattle, WA 98103
Country 121363 0
United States of America
Phone 121363 0
+18669653044
Fax 121363 0
Email 121363 0
[email protected]
Contact person for scientific queries
Name 121364 0
Margaret Wierman
Address 121364 0
Morair Medtech
401 N 36th St.
Suite 202
Seattle, WA 98103
Country 121364 0
United States of America
Phone 121364 0
+18669653044
Fax 121364 0
Email 121364 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data sets will not be analysed 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.