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Trial registered on ANZCTR


Registration number
ACTRN12618001805268
Ethics application status
Approved
Date submitted
31/10/2018
Date registered
6/11/2018
Date last updated
23/04/2019
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the changes in physiological function following bronchoscopic lung volume reduction treatment of chronic obstructive pulmonary disease (COPD)
Scientific title
The Physiological Changes Following Bronchoscopic Lung Volume Reduction Treatment for Chronic Obstructive Pulmonary Disease (COPD)
Secondary ID [1] 296435 0
None
Universal Trial Number (UTN)
U1111-1223-0145
Trial acronym
The EMphysema, PHYSiology, and exercISe responsE Trial (EMPHYSISE)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 310196 0
Emphysema
 310197 0
Respiratory physiology 310198 0
Cardiac Physiology 310199 0
Cor Pulmonale 310200 0
Pulmonary Vascular Resistance 310201 0
Exercise Physiology 310202 0
Condition category
Condition code
Respiratory 308943 308943 0 0
Chronic obstructive pulmonary disease
Cardiovascular 308944 308944 0 0
Diseases of the vasculature and circulation including the lymphatic system
Physical Medicine / Rehabilitation 308945 308945 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
2
Target follow-up type
Years
Description of intervention(s) / exposure
Examining the physiological changes following bronchoscopic lung volume reduction using endobronchial valves using the following investigations:
- Cardiopulmonary Exercise Test: VO2 max test (60mins including setup time)
- Cardiopulmonary Exercise Test: Constant Workrate (60mins including setup time)
- Cardiac Echocardiogram (30mins)
- Cardiac MRI (30-45mins)
- V/Q SPECT scanning (60 mins)
- Blood Serum Sampling of humoral and inflammatory biomarkers (5mins done on day of BLVR procedure at time of admission and at 3-month review post BLVR)

Investigations will occur at least 2 weeks prior to BLVR and then be repeated again 3 months after the BLVR procedure.

Who will be performing/administering assessments?:
CPETs - Respiratory physiology scientist with a supervising doctor overseeing testing
Cardiac Echocardiogram - Reference Cardiologist (co-investigator)
Cardiac MRI - Reference Radiographer, radiologist, and cardiologist (co-investigator)
V/Q SPECT - Reference Radiographer and nuclear physician (co-investigator)
Blood Serum sampling - Primary investigator
Intervention code [1] 312801 0
Not applicable
Comparator / control treatment
Participants will be their own comparator. Comparing pre-treatment results to post-intervention outcomes.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307955 0
A change in VO2 max based on a Cardiopulmonary Maximum Workrate Test
Timepoint [1] 307955 0
3 months following bronchoscopic lung volume reduction (BLVR) therapy
Primary outcome [2] 307975 0
A change in exercise endurance time based on a CPET Constant work rate test set at 75% of the maximum workload of the maximum effort CPET
Timepoint [2] 307975 0
3 months post-BLVR
Secondary outcome [1] 353454 0
A change in ventilatory dynamics on exertion shown by Ve/VCO2 slope with CPET
Timepoint [1] 353454 0
3 months post-BLVR
Secondary outcome [2] 353455 0
A change in pulmonary vascular resistance as shown by flow velocity measurements through the pulmonary artery trunk on 4D Cardiac MRI
Timepoint [2] 353455 0
3-months post BLVR
Secondary outcome [3] 353459 0
Changes in cardiac structure and function based on cardiac MRI findings including:
- Right ventricular end-diastolic and end-systolic volumes
- Measurement of RVEF
- Right ventricular mass
- Right and Left atrial volumes
- CMR-enabled measurement of left and right ventricular global longitudinal, circumferential and radial strain
- Velocity-encoded (VENC) derived flow measurement of pulmonary valvular flow.
Timepoint [3] 353459 0
3 months post BLVR
Secondary outcome [4] 353467 0
A change in systemic inflammation, as measured by expression of C-Reactive Protein (CRP) on serum sampling.
Timepoint [4] 353467 0
3 months post BLVR
Secondary outcome [5] 353547 0
A change in cardiac function based on echocardiographic findings, including:
- Right atrial volumes
- Right ventricular ejection fraction
- Interventricular septal wall thickness
- Right ventricular volume changes
- Estimated peak pulmonary artery pressure
Timepoint [5] 353547 0
3-months post-BLVR
Secondary outcome [6] 353548 0
A change in the humoral biomarker expression of Vascular Endothelial Growth Factor (VEGF) measured on serum sampling
Timepoint [6] 353548 0
3 months post-BLVR
Secondary outcome [7] 353587 0
A change in systemic inflammation, as measured by expression of Interleukin-6 (iL-6) on serum sampling.
Timepoint [7] 353587 0
3 months post-BLVR
Secondary outcome [8] 353588 0
A change in the humoral biomarker expression of Hypoxia-inducible Factor 1 alpha (HiF1a) measured on serum sampling
Timepoint [8] 353588 0
3 months post-BLVR

Eligibility
Key inclusion criteria
- Established diagnosis of COPD with hyperinflation: post-bronchodilator FEV1 <50% of predicted AND TLC > 100% AND RV>175%
- The absence of any collateral ventilation between target lobe and ipsilateral lobe, diagnosed with quantitative CT fissure integrity of >90% and confirmation of integrity with Chartis measurement.
- Age >18 and <75 at the time of enrolment.
- 6-min walk test distance >150m following successful completion of a pulmonary rehabilitation program (or equivalent program).
- No evidence of significant coexistent pulmonary pathology on HRCT
- Able to safely undergo sedation or general anesthesia and bronchoscopy
- Cessation of smoking for 3 months prior
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any patient deemed not suitable for EBV insertion based on internationally accepted best-practice guidelines. Considerations include:
- Significant co-existent pulmonary pathology
- Severe Hypercapnia (pCO2 > 60mmHg on room air)
- Unstable cardiovascular disease
- Severe heart failure: EF <35%
- Unstable cardiac arrhythmia, myocardial infarction or stroke within 6 months
- Severe PAH: RVSP >45mmHg
- Current Smoker
- 6MWT distance less than 150m post pulmonary rehabilitation or equivalent program
- FEV1 <15% predicted
- Any device or foreign object deemed unsafe for MRI (e.g. Pacemaker, shrapnel etc.)
- Pregnancy or potentially pregnant
- Egg or protein allergies

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis
As patients will be their own internal control, paired t-tests will be used for statistical analysis. This study aims to be a large case series report. For VO2 max previous studies have used an increase in work rate of 10W to be the minimal clinically important difference. Based on SA Health Lung Volume Reduction data, approximately 70% of treated patients are objective responders based on established MCIDs. Assuming alpha 0.05, and a power of 80%, we will require 46 participants to adequately power this study to show that lung volume reduction has a net positive effect on CPET output.
These values will also be compared with the healthy controls via the same statistical method.
To date, there is a paucity of data regarding the cardiac structural changes that occur following treatment of the pulmonary artery hypertension, let alone the changes following treatment of cor pulmonale. Currently, there is no consensus regarding MCID data regarding changes in RV volume or RV size and structure following treatment for PAH. This study will correlate the observed cardiac changes with the other physiological changes investigated. Paired-T tests will be used to compare the pre- and post BLVR changes in right ventricular volume and size.
The effects of BLVR on the VQDI will also be analysed. The pre and post VQDI of the target lobe, the ipsilateral untreated lobe and the contralateral lung will be compared with paired T test. A subanalysis will be to analyse the effect on lobar VQDI post BLVR among the responders and non responders.

Further Sub-group analysis, for all data, will be performed comparing the results of those who achieved a “successful” BLVR versus those that did not.
The changes in levels of expression of tested endothelial biomarkers will also be compared against a cohort of healthy control samples.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/12/2018
Actual
27/02/2019
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
31/03/2021
Actual
Sample size
Target
50
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 12312 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 12313 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 12314 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 12315 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [5] 12316 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 24547 0
5000 - Adelaide
Recruitment postcode(s) [2] 24548 0
5011 - Woodville
Recruitment postcode(s) [3] 24549 0
2170 - Liverpool
Recruitment postcode(s) [4] 24550 0
2109 - Macquarie Park
Recruitment postcode(s) [5] 24551 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 301035 0
Commercial sector/Industry
Name [1] 301035 0
PulmonX Australia
Country [1] 301035 0
Australia
Funding source category [2] 301070 0
Charities/Societies/Foundations
Name [2] 301070 0
Thoracic Society of Australia and New Zealand
Country [2] 301070 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
University of Adelaide
School of Medicine, Faculty of Health Sciences
North Terrace
ADELAIDE 5000
SOUTH AUSTRALIA
Country
Australia
Secondary sponsor category [1] 300630 0
Hospital
Name [1] 300630 0
The Royal Adelaide Hospital
Address [1] 300630 0
Royal Adelaide Hospital
1 Port Road
Adelaide 5000
SOUTH AUSTRALIA
Country [1] 300630 0
Australia
Other collaborator category [1] 280412 0
University
Name [1] 280412 0
University of South Australia
Address [1] 280412 0
University of South Australia
Dept of Physiotherapy
North Terrace
ADELAIDE 5000
SOUTH AUSTRALIA
Country [1] 280412 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301789 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301789 0
Ethics committee country [1] 301789 0
Australia
Date submitted for ethics approval [1] 301789 0
19/06/2018
Approval date [1] 301789 0
05/09/2018
Ethics approval number [1] 301789 0
HREC/18/CALHN/389

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

Contacts
Principal investigator
Name 88110 0
Dr Andrew Fon
Address 88110 0
Dept of Thoracic Medicine
Royal Adelaide Hospital
1 Port Road
ADELAIDE 5000
SOUTH AUSTRALIA
Country 88110 0
Australia
Phone 88110 0
+61 8 7074 0000
Fax 88110 0
Email 88110 0
andrew.fon@sa.gov.au
Contact person for public queries
Name 88111 0
Andrew Fon
Address 88111 0
Dept of Thoracic Medicine
Royal Adelaide Hospital
1 Port Road
ADELAIDE 5000
SOUTH AUSTRALIA
Country 88111 0
Australia
Phone 88111 0
+61 8 7074 0000
Fax 88111 0
Email 88111 0
andrew.fon@sa.gov.au
Contact person for scientific queries
Name 88112 0
Andrew Fon
Address 88112 0
Dept of Thoracic Medicine
Royal Adelaide Hospital
1 Port Road
ADELAIDE 5000
SOUTH AUSTRALIA
Country 88112 0
Australia
Phone 88112 0
+61 8 7074 0000
Fax 88112 0
Email 88112 0
andrew.fon@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All participants' recorded data will be made available, with any identifying patient names/labels removed.
When will data be available (start and end dates)?
Data will be available at the conclusion of the study, beginning 3 months following main results publication and ending 5 years after the first release.
Available to whom?
Researchers who provide a methodologically sound proposal.
Available for what types of analyses?
For the purposes of the primary study protocol, and possibly IPD Meta-analyses at the discretion of the primary investigator
How or where can data be obtained?
Access will be subject to approvals by the PI, pending need to sign a data access request/agreement


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.