Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12622001074785
Ethics application status
Approved
Date submitted
28/07/2022
Date registered
3/08/2022
Date last updated
4/08/2023
Date data sharing statement initially provided
3/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A prospective observational study assessing the impact of positive airway pressure therapy in patients with chronic obstructive pulmonary disease and obstructive sleep apnoea (overlap syndrome).
Scientific title
The effect of positive airway pressure therapy on cardiac remodeling, cardiovascular risk factors and neurocognitive function in patients with chronic obstructive pulmonary disease and obstructive sleep apnoea overlap syndrome.
Secondary ID [1] 307377 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
The REMAPS Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic obstructive pulmonary disease 326686 0
Obstructive sleep apnoea 326687 0
Cardiac remodeling 326688 0
Cardiovascular disease 327207 0
Cognitive impairment 327208 0
Condition category
Condition code
Respiratory 323926 323926 0 0
Chronic obstructive pulmonary disease
Respiratory 323927 323927 0 0
Sleep apnoea
Cardiovascular 323928 323928 0 0
Other cardiovascular diseases
Neurological 324381 324381 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a 3 month, prospective observational study to assess the effect of positive airway pressure (PAP) therapy on cardiac remodeling as assessed by cardiac magnetic resonance imaging (CMRI). PAP therapy will consist of either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) depending on the predominant feature of obstructive sleep apnoea (OSA) or chronic obstructive pulmonary disease (COPD) and the presence of hypercapnic respiratory failure and will be determined by the patient’s treating physician rather than the study investigators. Patients selected for the study will have overlap syndrome (OVS) and meet clinical criteria for initiating PAP therapy but have not yet commenced treatment. PAP therapy will be determinted by the patient's usual treating physician and only patients who agree to commence PAP therapy will be eligible to participate in this study. Patients who cease PAP therapy after enrolling in the study may still be included for the final analysis if they agree to continue in the study.

The secondary objective is to investigate whether PAP therapy also leads to improvement in other surrogate markers of cardiovascular (CV) risk, neurocognitive function, exercise capacity and quality of life scores.

Participants deemed suitable for entry into the study will be contacted and undergo
consent, randomization, and the following procedures at baseline and again after 3 months.
- CMRI will be performed by a radiologist and interpreted by an accredited cardiologist. It should take approximately 60 minutes to complete.
- Blood sampling for cardiac biomarkers (NT-pro-BNP, troponin, C-reactive peptide) will be performed by one of the study investigators and will take approximately 5 minutes
- Pulse wave analysis (PWA) will be performed by one of the study investigators and should take 10-15 minutes.
- Cognitive test battery will be performed by one of the study investigators and should take about 30 minutes
- 6 minute walk testing (6MWT) will be performed by one of the study investigators and should take about 10 minutes
- Quality of life (QoL) scores will be performed by one of the study investigators and should take about 30 minutes.
- cardiopulmonary coupling (CPC) analysis and quantitative EEG analysis will be performed on data collected during sleep study.

Patients will be treated for 3 months with PAP therapy, either CPAP or NIV. Their compliance and usage will be monitored remotely. Patients will also receive weekly phone calls to verify their compliance and ensure there are no issues with their PAP therapy or equipment.

End of 3 months:
Repeat cardiac MRI, blood sampling for cardiac biomarkers (NT-pro-BNP, troponin, CRP,
metabolic markers), PWA, cognitive test battery, 6MWT and QoL scores. CPC and quantitative
EEG analysis will be performed on data collected during sleep study.
Intervention code [1] 323806 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331734 0
Changes in right ventricular (RV) mass as measured by CMRI.
Timepoint [1] 331734 0
Measured at baseline and three months after positive airway pressure therapy.
Primary outcome [2] 332180 0
Changes in right ventricular remodeling index (RVRI) as measured by CMRI.
Timepoint [2] 332180 0
Measured at baseline and three months after positive airway pressure therapy.
Primary outcome [3] 332181 0
Changes in focal and diffuse myocardial fibrosis as measured by CMRI.
Timepoint [3] 332181 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [1] 410902 0
Changes in levels of serum cardiac biomarkers: NT-pro-BNP, troponin, CRP.
Timepoint [1] 410902 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [2] 410903 0
Changes in heart rate variability measured using electrocardiogram-based CPC during overnight polysomnography.
Timepoint [2] 410903 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [3] 410904 0
Changes in pulse wave velocity as measured by PWA.
Timepoint [3] 410904 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [4] 410905 0
Changes in neurocognitive function using mini-mental status examination (MMSE).
Timepoint [4] 410905 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [5] 410906 0
Changes in quantitative EEG measures of sleep microarchitecture will be assessed on the overnight polysomnography data using power spectral analysis and a sleep spindle detection algorithm.
Timepoint [5] 410906 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [6] 410907 0
Changes in 6-minute walk distance as measured by 6MWT.
Timepoint [6] 410907 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [7] 410908 0
Changes in subjective sleepiness as measured by Epworth Sleepiness Scale.
Timepoint [7] 410908 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [8] 412485 0
Sleep quality index measured using electrocardiogram-based CPC during overnight polysomnography.
Timepoint [8] 412485 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [9] 412486 0
Changes in arterial stiffness as measured by PWA.
Timepoint [9] 412486 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [10] 412487 0
Changes in neurocognitive function using montreal cognitive assessment (MoCA).
Timepoint [10] 412487 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [11] 412488 0
Changes in neurocognitive function using a computerised cognitive test battery modelled on conventional neuropsychological tests. Cognitive domains assessed include attention, concentration, visuospatial, working memory and executive functions. This test battery has been described in D'Rozario et al, Sleep 2022.
Timepoint [11] 412488 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [12] 412489 0
Changes in Functional Outcomes of Sleep Questionnaire.
Timepoint [12] 412489 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [13] 412490 0
Changes in quality of life assessed by the 36-item Short Form survey.
Timepoint [13] 412490 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [14] 412491 0
Changes in Pittsburgh Sleep Quality Index.
Timepoint [14] 412491 0
Measured at baseline and three months after positive airway pressure therapy.
Secondary outcome [15] 412492 0
Changes in emotional disturbance assessed using the Depression Anxiety Stress Scale 21.
Timepoint [15] 412492 0
Measured at baseline and three months after positive airway pressure therapy.

Eligibility
Key inclusion criteria
• Participants must be aged 40 years old or older.
• At least 10 pack-year smoking history.
• Spirometry demonstrating post bronchodilator FEV1/FVC less than the lower limits of normal (LLN) and FEV1 less than the LLN.
• Polysomnography (PSG) or level 2 home sleep study performed within the last 6 months of first medical visit demonstrating apnoea hypopnoea index (AHI) of equal to or greater than 30.
• Patient is not already on PAP therapy and the treating physician deems patient should start PAP therapy.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Unstable patients (COPD exacerbation within last 4 weeks or myocardial infarction or stroke within the last 6 weeks)
• Neuromuscular disease.
• Sleep disorders other than OSA.
• Patients who have a contraindication to or don’t tolerate CMRI or PAP therapy.
• Moderate or greater valvular heart disease.
• Renal insufficiency with eGFR<30 ml/min/1.73m2
• Unstable Malignancy.
• History of major psychiatric disorder in the last 12 months which is likely to affect adherence to trial protocol and follow up
• Willingness to provide informed consent and willingness to participate and comply with the study requirements.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We have selected the sample size of 20 patients after considering the available budget and the feasibility of a PhD study. Previous observational studies that have looked at the impact of PAP therapy on cardiac function and dimensions in patients with OSA have used similar numbers.

Paired t-tests or Wilcoxon’s paired tests will be used as appropriate to compare continuous variables before and after therapeutic intervention. Fisher’s exact test or Pearson’s chi-squared test will be used as appropriate to compare categorical data before and after therapeutic intervention. Linear regression will be used for subgroup analyses. A Statistical Analysis Plan with the exact coding to be used in R Studios will be prepared before data collection has finished.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/08/2022
Actual
20/09/2022
Date of last participant enrolment
Anticipated
1/09/2023
Actual
Date of last data collection
Anticipated
1/12/2023
Actual
Sample size
Target
20
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22569 0
Woolcock Institute of Medical Research - Glebe
Recruitment hospital [2] 22570 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 37820 0
2037 - Glebe
Recruitment postcode(s) [2] 37821 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 311656 0
University
Name [1] 311656 0
University of Sydney
Country [1] 311656 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 313428 0
None
Name [1] 313428 0
Address [1] 313428 0
Country [1] 313428 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311112 0
Sydney Local Health District Ethics Review Committee (RPAH Zone).
Ethics committee address [1] 311112 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 311112 0
Australia
Date submitted for ethics approval [1] 311112 0
12/07/2022
Approval date [1] 311112 0
25/07/2022
Ethics approval number [1] 311112 0
X22-0162 & 2022/ETH00929

Summary
Brief summary
COPD and OSA are the most prevalent respiratory diseases. Patients with both conditions termed overlap syndrome are at increased risk of dying from cardiac related problems. Positive airway pressure therapy are devices that stabilise the airway and assist with breathing. The aims of this study is to assess whether positive airway pressure therapy can reverse the negative consequences that occur in the heart of people with overlap syndrome and whether it can reduce their cardiovascular risk.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119982 0
Prof Brendon Yee
Address 119982 0
Department of Respiratory & Sleep Medicine
Level 11, Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 119982 0
Australia
Phone 119982 0
+61 0295156655
Fax 119982 0
Email 119982 0
[email protected]
Contact person for public queries
Name 119983 0
Dr Ben Nguyen
Address 119983 0
Department of Respiratory & Sleep Medicine
Level 11, Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 119983 0
Australia
Phone 119983 0
+61 0295156655
Fax 119983 0
Email 119983 0
[email protected]
Contact person for scientific queries
Name 119984 0
Dr Ben Nguyen
Address 119984 0
Department of Respiratory & Sleep Medicine
Level 11, Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 119984 0
Australia
Phone 119984 0
+61 0295156655
Fax 119984 0
Email 119984 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16762Ethical approval    384231-(Uploaded-28-07-2022-18-50-51)-Study-related document.pdf



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.