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Trial registered on ANZCTR


Registration number
ACTRN12619001309178p
Ethics application status
Not yet submitted
Date submitted
6/08/2019
Date registered
25/09/2019
Date last updated
1/09/2021
Date data sharing statement initially provided
25/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Bilevel Positive Airway Pressure To Air Trapping and Improve Sleep Quality in Chronic Obstructive Pulmonary Disease
Scientific title
Bilevel Positive Airway Pressure To Reduce Air Trapping and Improve Sleep Quality in Chronic Obstructive Pulmonary Disease
Secondary ID [1] 298742 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 313673 0
Poor Sleep Quality 313943 0
Condition category
Condition code
Respiratory 312086 312086 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
COPD patients with poor sleep will attend an initial screening visit to assess eligibility based on lung function and other sleep characteristics. Eligible participants will be invited to return to the laboratory in which they will undergo two titrations of Bilevel non-invasive ventilation. During the first titration, inspiratory pressure will be increased from 4cmH2O up to 24cmH2O, in increments of 4cmH2O. In the second titration, the ratio of inspiratory time to expiratory time will be increased from 1:2 to 1:4, with the expiratory time ratio increased in increments of 0.5. Expiratory pressure will be set at 4cmH2O during both titrations.

The two Bilevel titrations will occur over a 2 hour period. Lung function will be measured at each Bilevel setting with the next step in the titration begun after completion of lung function. The titration will be performed by a researcher.

Participants will then undergo two overnight polysomnography sleep studies involving either Bilevel ventilation or no breathing assistance (control) in random order. These visits will be at least 7 days apart. During the six nights prior to the sleep study with Bilevel, participants will be asked to use Bilevel at home, with adherence monitored by device analytics. The Bilevel inspiratory pressure will be set in order to reduce functional residual capacity by 15% of predicted (calculated from Visit 1) with expiratory pressure set at 4cmH2O.
Intervention code [1] 315025 0
Treatment: Other
Comparator / control treatment
The control will be normal sleep conditions without non-invasive ventilation ie no breathing assistance.
Control group
Active

Outcomes
Primary outcome [1] 320733 0
This outcome will assess the effect of Bilevel ventilator settings on intrinsic positive end-expiratory pressure (iPEEP), as measured by the oesophageal balloon test. iPEEP reflects the amount of gas trapped within the lung. Oesophageal and gastric pressures will be measured by a conventional balloon catheter system inserted via the nose after topical anesthesia. Pressure and flow will be measured at the mouth. This will allow calculation of transpulmonary pressure as the difference between oesophageal pressure and mouth pressure. iPEEP will be measured as the plateau in transpulmonary pressure during a sustained maximal inspiratory effort against an occluded mouthpiece.
Timepoint [1] 320733 0
iPEEP will be measured at the first study visit at baseline and after each level of Bilevel titration (inspiratory or inspiratory:expiratory time).
Primary outcome [2] 320976 0
This outcome will measure the effect of Bilevel ventilator settings on end-expiratory lung volume, as a measurement of the degree of hyperinflation. End-expiratory lung volume will be measured using Respiratory Inductive Plethysmography. This involves placing two sinusoidal shielded wires embedded in elastic material around the rib cage and abdomen.
Timepoint [2] 320976 0
iPEEP will be measured at the first study visit at baseline and after each level of Bilevel titration (inspiratory or inspiratory:expiratory time).
Secondary outcome [1] 372655 0
Arousal index measured during full overnight polysomnography.
Timepoint [1] 372655 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [2] 373585 0
Total Sleep Time measured during full overnight polysomnography.
Timepoint [2] 373585 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [3] 373590 0
Sleep Efficiency (time spent asleep as percent of Total Sleep Time) measured during full overnight polysomnography.
Timepoint [3] 373590 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [4] 373591 0
Apnoea-Hypopnoea Index measured during full overnight polysomnography.
Timepoint [4] 373591 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [5] 373592 0
Time Awake After Sleep Onset measured during full overnight polysomnography.
Timepoint [5] 373592 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [6] 373593 0
Quantity of Non-REM Sleep measured during full overnight polysomnography.
Timepoint [6] 373593 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.
Secondary outcome [7] 373594 0
Quantity of REM sleep measured during full overnight polysomnography.
Timepoint [7] 373594 0
This will be measured at Visit 2 and 3, which will occur within 6 weeks of visit one and at least 7 days apart.

Eligibility
Key inclusion criteria
1) Diagnosis of COPD with smoking history of >10 pack years
2) Poor sleep quality (Pittsburgh Sleep Quality Index >5)
3) Hyperinflation (functional residual capacity or residual volume >130% predicted)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Hypercapneic respiratory failure
2) Respiratory pathologies other than COPD
3) Moderate-severe Obstructive Sleep Apnoea (based on polysomnogram)
4) Insomnia (based on Insomnia Severity Index questionnaire)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be kept on a computer. The holder of the allocation schedule will not be involved in determining subject eligibility and will provide the allocation after the completion of Visit 1.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be computer generated in blocks of 8 participants by computerised sequence generation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study will be powered to detect a correlation between end-expiratory lung volume, and the difference between Bilevel inspiratory pressure and intrinsic Positive End-Expiratory pressure (iPEEP). Guerin et al reported a correlation co-efficient of 0.8 for the relationship between end-expiratory lung volume and the difference between CPAP pressure and iPEEP (PEEP - iPEEP). Similarly, van den Berg et al reported a correlation coefficient of -0.7 between inspiratory work of breathing and the difference between CPAP and iPEEP. Therefore, we conservatively estimate a correlation coefficient of 0.65 so that we would require 16 participants (80% power, 0.05 significance level). Our pilot data suggests that the prevalence of OSA in COPD is up to 40%, so that we will need to screen 27 patients in order to recruit 16 eligible participants.

Data will be checked for normality. We will use regression analyses adjusting for repeat measures in order to determine the relationship between Bilevel inspiratory pressure and end-expiratory lung volume. Similarly, we will use repeat measures regression analyses to determine the relationship between Bilevel inspiratory:expirtory time and en-expiratory lung volume. Paired analyses will then be used to compare sleep parameters between the control and Bilevel conditions.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
COVID-19 restrictions on sleep studies and use of non-invasive ventilation has meant that we have had to redesign the study.
Date of first participant enrolment
Anticipated
9/12/2019
Actual
Date of last participant enrolment
Anticipated
2/05/2022
Actual
Date of last data collection
Anticipated
30/05/2022
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14243 0
Woolcock Institute of Medical Research - Glebe
Recruitment hospital [2] 14244 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 14443 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 27236 0
2037 - Glebe
Recruitment postcode(s) [2] 27241 0
2050 - Camperdown
Recruitment postcode(s) [3] 27457 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 303299 0
Charities/Societies/Foundations
Name [1] 303299 0
American Thoracic Society/ResMed Research Fellowship
Country [1] 303299 0
United States of America
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
432 Glebe Point Road
Glebe NSW 2037
Country
Australia
Secondary sponsor category [1] 303554 0
None
Name [1] 303554 0
Address [1] 303554 0
Country [1] 303554 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 303830 0
Sydney Local Health District - RPA
Ethics committee address [1] 303830 0
Ethics committee country [1] 303830 0
Australia
Date submitted for ethics approval [1] 303830 0
04/11/2019
Approval date [1] 303830 0
Ethics approval number [1] 303830 0

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

Contacts
Principal investigator
Name 94962 0
Dr David Chapman
Address 94962 0
Woolcock Institute of Medical Research
Level 4
431 Glebe Point Road,
Glebe, NSW, 2037
Country 94962 0
Australia
Phone 94962 0
+61 2 9114 0413
Fax 94962 0
Email 94962 0
david.chapman@woolcock.org.au
Contact person for public queries
Name 94963 0
David Chapman
Address 94963 0
Woolcock Institute of Medical Research
Level 4,
431 Glebe Point Road,
Glebe, NSW, 2037
Country 94963 0
Australia
Phone 94963 0
+61 2 9114 0413
Fax 94963 0
Email 94963 0
david.chapman@woolcock.org.au
Contact person for scientific queries
Name 94964 0
David Chapman
Address 94964 0
Woolcock Institute of Medical Research
Level 4
431 Glebe Point Road,
Glebe, NSW, 2037
Country 94964 0
Australia
Phone 94964 0
+61 2 9114 0413
Fax 94964 0
Email 94964 0
david.chapman@woolcock.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.