Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000379213
Ethics application status
Approved
Date submitted
6/03/2018
Date registered
14/03/2018
Date last updated
13/07/2021
Date data sharing statement initially provided
13/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing auto-titrating continuous positive airway pressure device with fixed continuous positive airway pressure device in improvement in hypercapnia among patients with obesity hypoventilation syndrome
Scientific title
Assessing the Efficacy of Auto-titrating versus Fixed Continuous Positive Airway Pressure in Obesity Hypoventilation Syndrome
Secondary ID [1] 293727 0
None
Universal Trial Number (UTN)
U1111-1207-3374
Trial acronym
OHS-APAP Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity Hypoventilation Syndrome 306096 0
Sleep Apnoea 306997 0
Condition category
Condition code
Respiratory 305219 305219 0 0
Sleep apnoea
Diet and Nutrition 306090 306090 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Exposure Group: Auto-titrating CPAP device (Phillips Dreamstation/Resmed Airsense 10), this uses an algorithm to adjust the delivered positive airway pressure according to the detected airflow obstruction during sleep.

CPAP therapy will be delivered using a nasal or full face mask interface. All subjects will have mask fitting performed by sleep technicians to ensure optimal interface is used for the duration of the study.

All subjects will receive mask and CPAP device education from sleep technicians as per usual clinical care. The sleep technicians are employed by Royal Prince Alfred Respiratory and Sleep Medicine unit with appropriate accreditation.

Subjects will receive clinical support from sleep physicians during individual clinical reviews as per usual care of patients with obesity hypoventilation syndrome.

Subjects will be provided their allocated therapy to be used during sleep every night, in the participant's home, for a period of 3 months for assessment of primary outcome.

The delivered pressure will be at an autoset range of 8-20cmH2O. They will have an overnight sleep study on their loaned auto-titrating CPAP device. This pressure range is expected to resolve most airway obstruction events encountered in our study subjects.

CPAP adherence will assessed. The data is recorded in a data chip in each CPAP device. This data will be downloaded by sleep technicians at the end of study (3months) for assessment of CPAP compliance. This is usual standard of care.
Intervention code [1] 299980 0
Treatment: Devices
Comparator / control treatment
Comparator group - fixed CPAP device (Phillips Dreamstation/Resmed Airsense 10), this will deliver a fixed pressure throughout the night of sleep. (standard care)

CPAP therapy will be delivered using a nasal or full face mask interface. All subjects will have mask fitting performed by sleep technicians to ensure optimal interface is used for the duration of the study.

All subjects will receive mask and CPAP device education from sleep technicians as per usual clinical care. The sleep technicians are employed by Royal Prince Alfred Respiratory and Sleep Medicine unit with appropriate accreditation.

Subjects will receive clinical support from sleep physicians during individual clinical reviews as per usual care of patients with obesity hypoventilation syndrome.

Subjects will be provided their allocated therapy to be used during sleep every night, in the participant's home, for a period of 3 months for assessment of primary outcome.

The delivered pressure will be pre-determined during an overnight CPAP titration sleep study. This is to ensure that optimal CPAP therapy is delivered for the duration of the study and also is the standard of care.

CPAP adherence will assessed. The data is recorded in a data chip in each CPAP device. This data will be downloaded by sleep technicians at the end of study (3months) for assessment of CPAP compliance. This is usual standard of care.
Control group
Active

Outcomes
Primary outcome [1] 304375 0
Efficacy of CPAP therapy:
Change in awake paCO2 on arterial blood gas analysis
Timepoint [1] 304375 0
At 1 months after intervention commencement
At 3 months after intervention commencement (primary timepoint)
Secondary outcome [1] 341762 0
Change in cardiovascular markers:
High sensitive troponin on serum assay
Timepoint [1] 341762 0
3 months after commencement of intervention
Secondary outcome [2] 341763 0
Change in quality of life and sleepiness:
Epworth Sleepiness Score
Timepoint [2] 341763 0
3 months after commencement of intervention
Secondary outcome [3] 341764 0
Treatment compliance:
Percentage of days greater than 4 hours of CPAP use via data download
Timepoint [3] 341764 0
3 months after commencement of intervention
Secondary outcome [4] 341765 0
Residual respiratory events on CPAP therapy:
Apnoea-hypopnea index data from CPAP device download
Timepoint [4] 341765 0
3 months after commencement of intervention
Secondary outcome [5] 341766 0
Change in cardiovascular markers:
N-terminal-pro b-type natriuretic peptide on serum assay
Timepoint [5] 341766 0
3 months after commencement of intervention
Secondary outcome [6] 341767 0
Change in cardiovascular markers:
C-reactive protein on serum assay
Timepoint [6] 341767 0
3 months after commencement of intervention
Secondary outcome [7] 341768 0
Change in cardiovascular markers:
HbA1c on serum assay
Timepoint [7] 341768 0
3 months after commencement of intervention
Secondary outcome [8] 341769 0
Change in cardiovascular markers:
Lipid profile (HDL, LDL, Total Cholesterol) on serum assay
Timepoint [8] 341769 0
3 months after commencement of intervention
Secondary outcome [9] 341770 0
Change in quality of life and sleepiness:
Functional Outcomes of Sleep Questionnaire
Timepoint [9] 341770 0
3 months after commencement of intervention
Secondary outcome [10] 341773 0
Change in quality of life and sleepiness:
Severe Respiratory Insufficiency Questionnaire
Timepoint [10] 341773 0
3 months after commencement of intervention
Secondary outcome [11] 343927 0
Efficacy of CPAP therapy:
Percentage sleep time less than oxygen saturation of 90% while on allocated CPAP therapy from CPAP device download
Timepoint [11] 343927 0
1 months after commencement of intervention
Secondary outcome [12] 343928 0
Change in cardiovascular markers:
Augmentation index from analysis of brachial artery pulse wave using a pulse wave analyser (AtCor, SphygmoCor XCEL)
Timepoint [12] 343928 0
3 months after commencement of intervention

Eligibility
Key inclusion criteria
• BMI>30kg.m-2
• Daytime respiratory failure with a PaCO2>45mmHg (OHS group)
• pH is in the normal range at admission (7.35-7.45)
• Treatment naïve of long-term positive airway pressure device i.e. the patient has not been using CPAP in the past 12 months.
• AHI>/= 30 events per hour
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Presence of any other condition that may contribute to hypoventilation including neuromuscular disease, chest wall abnormalities, respiratory depressant medications, COPD or an FEV1/FVC ratio of <0.7
• Uncontrolled medical or psychiatric conditions
• Any pre-existing heart failure with reduced ejection fraction
• Any pre-existing CVA/TIA
• Decompensated right heart failure
• Not proficient in English
• Inability to provide informed consent
• PaCO2 >60mmHg

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Prior to treatment, the baseline measurements of both groups will be expressed as mean and SD or percentages with 95% CIs and compared using Student’s t-test and X2 analysis. Linear mixed models will be used to examine the fixed effects of group (auto-titrating CPAP or fixed CPAP), time (baseline, 1 and 3 months after commencing treatment) and their interaction, on arterial blood gas analysis, cardiovascular outcomes, quality of life measurements and compliance. Mixed effects modeling will be used to control for differences in compliance.

Using a margin for non-inferiority of 5mmHg paCO2, a Type I error of 5%, a Type II error of 20%, the sample size required is over 200. There is insufficient data on secondary outcomes to perform power analysis. As this is designed as a pilot study, a total of 40 patients will be studied with 20 patients randomised to each treatment arm.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/04/2018
Actual
20/08/2018
Date of last participant enrolment
Anticipated
22/08/2022
Actual
Date of last data collection
Anticipated
24/11/2022
Actual
Sample size
Target
40
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9695 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 18464 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 298342 0
Hospital
Name [1] 298342 0
Royal Prince Alfred Hospital
Country [1] 298342 0
Australia
Primary sponsor type
Individual
Name
Yizhong Zheng
Address
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 297461 0
Individual
Name [1] 297461 0
A/Prof Brendon Yee
Address [1] 297461 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country [1] 297461 0
Australia
Other collaborator category [1] 279984 0
Individual
Name [1] 279984 0
Dr Amanda Piper
Address [1] 279984 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country [1] 279984 0
Australia
Other collaborator category [2] 279985 0
Individual
Name [2] 279985 0
Dr Keith Wong
Address [2] 279985 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country [2] 279985 0
Australia
Other collaborator category [3] 279986 0
Individual
Name [3] 279986 0
Prof Ron Grunstein
Address [3] 279986 0
The Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country [3] 279986 0
Australia
Other collaborator category [4] 279987 0
Individual
Name [4] 279987 0
Dr Craig Phillips
Address [4] 279987 0
The Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037 Sydney, Australia
Country [4] 279987 0
Australia
Other collaborator category [5] 279988 0
Individual
Name [5] 279988 0
Dr David Wang
Address [5] 279988 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country [5] 279988 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299335 0
Research Ethics and Governance Office of Sydney Local Health District
Ethics committee address [1] 299335 0
Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Ethics committee country [1] 299335 0
Australia
Date submitted for ethics approval [1] 299335 0
26/03/2018
Approval date [1] 299335 0
30/05/2018
Ethics approval number [1] 299335 0

Summary
Brief summary
The aim of our study is to examine the efficacy and safety of auto-titrating continuous positive airway pressure devices (CPAP) when compared to standard of care fixed-pressure CPAP in patients with obesity hypoventilation syndrome with concurrent severe obstructive sleep apnoea who are suitable for CPAP therapy.

We hypothesis that auto-titrating CPAP is not inferior to CPAP with respect to improvements in ventilatory failure (measured by arterial CO2 tension), sleep quality, quality of life as well as a number of cardiovascular biomarkers.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2478 2478 0 0
/AnzctrAttachments/374259-OHS APAP fCPAP protocol v4 March 6 2018.pdf (Protocol)
Attachments [2] 2479 2479 0 0
/AnzctrAttachments/374259-Project information APAP-OHS version 1 March 6 2018.pdf (Participant information/consent)
Attachments [3] 2480 2480 0 0
/AnzctrAttachments/374259-CONSENT APAP-OHS Project Participant Consent Form Nov 2017.pdf (Participant information/consent)

Contacts
Principal investigator
Name 80094 0
Dr Yizhong Zheng
Address 80094 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country 80094 0
Australia
Phone 80094 0
+61 2 91140497
Fax 80094 0
Email 80094 0
[email protected]
Contact person for public queries
Name 80095 0
Dr Yizhong Zheng
Address 80095 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country 80095 0
Australia
Phone 80095 0
+61 2 91140497
Fax 80095 0
Email 80095 0
[email protected]
Contact person for scientific queries
Name 80096 0
Dr Yizhong Zheng
Address 80096 0
Department of Respiratory and Sleep Medicine
50 Missenden Rd
Camperdown NSW 2050
Country 80096 0
Australia
Phone 80096 0
+61 2 91140497
Fax 80096 0
Email 80096 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?

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.