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Trial registered on ANZCTR


Registration number
ACTRN12619000743167p
Ethics application status
Not yet submitted
Date submitted
7/05/2019
Date registered
20/05/2019
Date last updated
20/05/2019
Date data sharing statement initially provided
20/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study of Video Assisted Thoracic Surgery (VATS) fissure completion prior to Zephyr® Endobronchial Valve insertion for severe Chronic Obstructive Pulmonary Disease (COPD) in patients with COllateral VEntilation
Scientific title
A pilot study of Video Assisted Thoracic Surgery (VATS) fissure completion prior to Zephyr® Endobronchial Valve insertion for severe Chronic Obstructive Pulmonary Disease (COPD) in patients with COllateral VEntilation
Secondary ID [1] 298177 0
Nil known
Universal Trial Number (UTN)
U1111-1232-9973
Trial acronym
COVE study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic COPD 312755 0
Condition category
Condition code
Respiratory 311248 311248 0 0
Chronic obstructive pulmonary disease
Surgery 311266 311266 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is investigating two separate surgeries to be used in conjunction with each other, in a subset of patients with chronic obstructive pulmonary disease (COPD). The surgical technique involved is video assisted thorascopic surgery (VATS). In this study, VATS will be used as an initial surgical procedure, to close air leaks between lung compartments (fissure completion) of participants with COPD. After this procedure, participants will undergo a second surgery, which will involve implanting a Zephyr Valve, into the most diseased part of the lung to stop inhaled air from getting to that part of the lung. The Zephyr Valve is currently approved for use in COPD patients that do not have air leaks between the lung compartments, however it has not previously been used in patients requiring fissure closure. This study will be examining whether it is safe and effective to undergo VATS fissure completion and then 4 weeks later, undergo the Zephyr Valve insertion. Thoracic Surgeons will be performing both procedures. The duration of the VATS procedure will be approximately 2 hours and the duration of the Zephyr Valve insertion will be approximately 1 - 1.5 hours.
Intervention code [1] 314403 0
Treatment: Surgery
Intervention code [2] 314404 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319992 0
Absolute change from pre-operative baseline at 6 months for Residual Volume (RV) as assessed by plethysmography .
Timepoint [1] 319992 0
6-months post valve implant.
Secondary outcome [1] 370124 0
Absolute change from pre-operative baseline at 6 months for Forced Vital Capacity (FVC)
as assessed by spirometry.
Timepoint [1] 370124 0
6-months post valve implant.
Secondary outcome [2] 370125 0
Absolute change from pre-operative baseline at 6 months for FEV1/FVC ratio as assessed by spirometry.
Timepoint [2] 370125 0
6-months post valve implant.
Secondary outcome [3] 370126 0
Absolute change from pre-operative baseline at 6 months for Total Lung Capacity (TLC) as assessed by six minute walk test..
Timepoint [3] 370126 0
6 months post valve implant
Secondary outcome [4] 370127 0
Absolute change from pre-operative baseline at 6 months for Exercise capacity by Six-minute walk test (6MWT)
Timepoint [4] 370127 0
6 months post valve implant
Secondary outcome [5] 370128 0
Absolute change from pre-operative baseline at 6 months for Quality of life as assessed by the St George’s Respiratory Questionnaire (SGRQ)
Timepoint [5] 370128 0
6 months post valve implant
Secondary outcome [6] 370129 0
Absolute change from pre-operative baseline at 6 months for Dyspnoea as assessed by the Modified Medical Research Council Dyspnoea Score (mMRC)
Timepoint [6] 370129 0
6 months post valve implant
Secondary outcome [7] 370130 0
Percent mean change from pre-operative baseline at 6 months for Forced Expiratory Volume in 1 second (FEV1) as assessed by spirometry.
Timepoint [7] 370130 0
6 months post valve implant.

Eligibility
Key inclusion criteria
1. Subject is willing and able to provide informed consent and to participate in the study.
2. Subject is greater than or equal to 40 years of age.
3. Subject has a diagnosis of severe or very severe homogenous or heterogeneous COPD (GOLD classification1).
4. Subject has a post bronchodilator FEV1 of greater than or equal to 15% and less than or equal to 50%.
5. Subject has TLC > 100% predicted.
6. Subject has RV > 175% predicted.
7. Subject has a normal dobutamine stress echocardiogram.
8. Subject has sufficient exercise tolerance i.e. 6MWT is greater than or equal to 150m and less than or equal to 450m.
9. Subject has an incomplete lobar fissure i.e. < 90%, as confirmed by CT evaluation of lung fissures.
10. Collateral ventilation confirmed as assessed by Chartis Assessment (to be confirmed during first procedure/operation)
11. Subject has stopped smoking for at least 8 weeks prior to entering the study as confirmed by carboxyhaemoglobin or cotinine levels.
12. Subject is up to date with preventive vaccinations including seasonal influenza vaccine and pneumococcal vaccine consistent with the Victorian Department of Health and Human Services Immunisation Schedule Guidelines (updated March 2018).
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has a history of previous thoracotomy, lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior pleurodesis, or prior endobronchial lung volume reduction therapy of any form.
2. Subject has an acute COPD exacerbation.
3. Subject has evidence of active respiratory infection.
4. Subject has a post bronchodilator FEV1 < 15%.
5. Subject has a DLCO < 20%.
6. Subject has a history of recurrent clinically significant respiratory infections, defined as three (3) or more COPD exacerbations requiring hospitalisation during the 12 months prior to study enrolment (ICF signature page).
7. Subject has severe gas exchange abnormalities as defined by any one of the following:
a. PaCO2 > 60 mmHg
b. PaO2 < 45 mmHg on room air
c. SpO2 < 90% on less than or equal to 4 L/min supplemental O2 at rest
8. Subject use of systemic steroids > 20mg/day or equivalent and/or immunosuppressive agents in the 4 weeks prior to procedure.
9. Subject unable to temporarily interrupt use of heparins or oral anticoagulants or antiplatelet agents, excluding aspirin.
10. Subject’s pre-operative CT scan indicates the presence of any of the following radiological abnormalities:
a. Pulmonary nodule is greater than or equal to 0.8 cm in diameter (does not apply if present for 2 years or more without increase in size or if proven benign by biopsy/PET).
b. Radiological picture consistent with active pulmonary infection, e.g. unexplained parenchymal infiltrate.
c. Giant bullae > 30% of the volume of either lung.
d. Significant interstitial lung disease.
e. Significant pleural disease.
11. Subject’s baseline ECG demonstrates clinically significant arrhythmias or conduction abnormalities.
12. Clinically significant asthma (reversible airway obstruction), chronic bronchitis or bronchiectasis.
13. Subject has a known diagnosis of alpha-1 antitrypsin deficiency.
14. Subject is classified as having “likely” pulmonary hypertension defined as tricuspid regurgitation velocity > 3.4m/s and/or pulmonary artery peak systolic pressure > 45 mmHg on echocardiogram or a previous formal diagnosis of pulmonary hypertension on right heart catheterization.
15. Subject has suspected significant coronary artery disease defined as regional wall motion abnormalities on dobutamine stress echocardiogram.
16. Subject is classified as being at major cardiac risk with the presence of unstable coronary syndromes (i.e. unstable or severe angina or recent myocardial infarct), decompensated heart failure, significant arrhythmias or severe valvular disease, which warrants intensive management of the condition in accordance with current guidelines on perioperative cardiovascular risk.

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)
Efficacy
Statistical methods / analysis
Descriptive statistical analysis of patient demographics and baseline clinicopathological characteristics will be reported as means (± Standard Deviation) or medians where appropriate. Pre and post-operative changes in lung function tests, lung volumes and exercise tolerance will be reported as percentage change from baseline.
Inferential statistical analysis, including but not limited to paired t-tests, will be used to compare and determine statistically significant change in primary and secondary outcome measures following fissure completion and insertion of Zephyr Valves. A p-value < 0.05 will be considered the threshold for statistical significance. Specifically, statistically significant change will be determined for pre- and post-operative measures of:
1. Forced Expiratory Volume in 1 second (FEV1)
2. Forced Vital Capacity (FVC)
3. FEV1/FVC ratio (%)
4. Total Lung Capacity (TLC)
5. Residual Volume (RV)
6. Exercise capacity by Six-minute walk test (6MWT)
7. Quality of life as assessed by the St George’s Respiratory Questionnaire (SGRQ)
8. Dyspnoea as assessed by the Modified Medical Research Council Dyspnoea Score (mMRC)

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13712 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 13713 0
St Vincent's Private Hospital - Fitzroy
Recruitment postcode(s) [1] 26408 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 302712 0
Commercial sector/Industry
Name [1] 302712 0
Pulmonx Australia Pty. Ltd.
Address [1] 302712 0
65 York Street Sydney, NSW 2000 Australia
Country [1] 302712 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Pulmonx Australia Pty. Ltd.
Address
65 York Street Sydney, NSW 2000 Australia
Country
Australia
Secondary sponsor category [1] 302640 0
None
Name [1] 302640 0
Address [1] 302640 0
Country [1] 302640 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 303322 0
St Vincent's Hospital Melbourne HREC
Ethics committee address [1] 303322 0
41 Victoria Pde, Fitzroy VIC 3065
Ethics committee country [1] 303322 0
Australia
Date submitted for ethics approval [1] 303322 0
30/05/2019
Approval date [1] 303322 0
Ethics approval number [1] 303322 0

Summary
Brief summary
AIM: To evaluate the safety and efficacy of VATS fissure completion (closing of air passage between lobes of the lung) followed by insertion of Zephyr Valves on improving the clinical status of participants with severe Chronic Obstructive Pulmonary Disease who have collateral ventilation (air moving between lobes).

PARTICIPANTS: 20 participants at SVHM and SVPH over 24 months.

METHOD: Participants will undergo two surgical procedures. The first procedure will be VATS fissure completion followed by CT assessment to ensure successful fissure completion. If successful, participants will undergo a second procedure 4 weeks later for insertion of the Zephyr Valve. Participants will be followed up over a 6 month period.

EXPECTED OUTCOMES:
Assessment of absolute change from pre-operative baseline at 6 months for:
a. Residual Volume (RV)
b. Forced Vital Capacity (FVC)
c. FEV1/FVC ratio
d. Total Lung Capacity (TLC)
e. Exercise capacity by Six-minute walk test
f. Quality of life (SGRQ)
g. Dyspnoea score
Percent mean change from pre-operative baseline at 6 months
h. Forced Expiratory Volume in 1 second (FEV1)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93270 0
Mr Naveed Alam
Address 93270 0
St Vincent's Hospital Melbourne
Department of Cardiothoracics
41 Victoria Pde
Fitzroy VIC 3065
Country 93270 0
Australia
Phone 93270 0
+613 9231 2211
Fax 93270 0
+613 9231 4616
Email 93270 0
nzalam@gmail.com
Contact person for public queries
Name 93271 0
Ms Jane Mack
Address 93271 0
St Vincent's Hospital Melbourne
Department of Cardiothoracics
41 Victoria Parade
Fitzroy VIC 3065
Country 93271 0
Australia
Phone 93271 0
+613 9231 4615
Fax 93271 0
+613 9231 4616
Email 93271 0
jane.mack@svha.org.au
Contact person for scientific queries
Name 93272 0
Mr Naveed Alam
Address 93272 0
St Vincent's Hospital Melbourne
Department of Cardiothoracics
41 Victoria Parade
Fitzroy VIC 3065
Country 93272 0
Australia
Phone 93272 0
+613 9231 2211
Fax 93272 0
+613 9231 4616
Email 93272 0
nzalam@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To protect patient confidentiality.
What supporting documents are/will be available?
No other documents available
Summary results
No Results