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Trial registered on ANZCTR


Registration number
ACTRN12611000874910
Ethics application status
Approved
Date submitted
15/08/2011
Date registered
16/08/2011
Date last updated
23/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimal Therapy for Obesity Hypoventilation Syndrome
Scientific title
A comparison of the effect of bi-level ventilatory support versus continuous positive airway pressure on the rates of treatment failure in patients with stable obesity hypoventilation syndrome
Secondary ID [1] 262806 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity hypoventilation syndrome 270512 0
Condition category
Condition code
Respiratory 270675 270675 0 0
Other respiratory disorders / diseases
Diet and Nutrition 270728 270728 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two commonly used non-invasive ventilation strategies in the respiratory management of patients with stable Obesity Hypoventilation Syndrome will be compared.
i) Bilevel PAP (positive airway pressure): use of bilevel ventilation set in a spontaneous-timed mode versus
ii) CPAPplus: Initial treatment with continuous positive airway pressure (CPAP), with progressive escalation of ventilatory support in case of treatment failure to spontaneous bilevel PAP and then bilevel in the spontaneous-timed mode if needed.
Note
i) Bilevel PAP involves the delivery of positive pressure through a nasal mask. The pressure delivered during inspiration is higher than that during expiration. These pressures act to "splint" the upper airway open and to increase the size of each assisted breath. The pressures used are estimated during a daytime familiarisation trial and confirmed during an overnight sleep study. The mask and device are to be used every night during sleep throughout the study period, ie 12 months. The delivered pressures will be in the range of 4-30cm H2O as observed in usual clinical practice.

ii) CPAP involves the delivery of a constant positive pressure through a nasal mask. The pressure delivered is constant across both inspiration and expiration. This pressure act to "splint" the upper airway open during sleep. The pressures used are estimated during a daytime familiarisation trial and confirmed during an overnight sleep study. The mask and device are to be used every night throughout the study period, ie 12 months. The delivered pressures will be in the range of 4-30cm H2O as observed in usual clinical practice.

Primary endpoint will be made at 3 months, with secondary endpoint at 12 months
Intervention code [1] 269154 0
Treatment: Other
Intervention code [2] 269195 0
Treatment: Devices
Comparator / control treatment
As above. Comparison of two different, current treatment strategies
Control group
Active

Outcomes
Primary outcome [1] 269394 0
Treatment failure defined as any one or more of the following;
a) Failure of awake PaCO2 to fall below 60mmHg within 3 months of commencing treatment or a rise of >10mmHg in daytime, awake PaCO2 at any time compare to that at randomization
b) Admission to hospital for respiratory deterioration (worsening respiratory failure, dyspnoea, right heart failure or severe sleepiness)
c) The patient abandons or is non-adherent with PAP therapy, defined as average nightly use <2hrs/night since last review, on 2 consecutive reviews (ie persisting after efforts to trouble shoot reasons for poor adherence).
Timepoint [1] 269394 0
Three and 12 months
Secondary outcome [1] 287541 0
Changes in awake blood gases
Timepoint [1] 287541 0
one, three and 12 months
Secondary outcome [2] 287542 0
Treatment compliance. This will be assessed by reading the "time at pressure" data from the positive pressure device. These data are automatically logged by the devices.
Timepoint [2] 287542 0
one, three and 12 months
Secondary outcome [3] 287543 0
Healthcare utilization and need for hospital admissions. Detailed questionnaire data will be collected monthly regarding participants use of health services. The economic evaluation proposed here is a within-trial analysis and will rely primarily on direct observation of treatment compliance, hospitalisations, healthcare utilization and quality of life in the trial population. All of these data will be gathered within the trial (monthly telephone calls, local hospital records, compliance data recorded by the bilevel device and quality of life questionnaires completed by participants). Results from the economic evaluation will be expressed as additional costs (savings) per SRI responder and costs(savings) per QALY gained.
Timepoint [3] 287543 0
one, three and 12 months
Secondary outcome [4] 287544 0
Changes in quality of life and sleepiness
Quality of life (QoL) - This will be measured with two questionnaires. The first is the Severe Respiratory Insufficiency (SRI) questionnaire; a disease specific QoL measure, specifically for use in people with chronic respiratory failure. The SF-36 is a generic health-related quality of life measure. The SF-36 data will also be transformed into the SF6D to calculate health utility values (and quality-adjusted life years) for the economic evaluation.
Daytime sleepiness - The Epworth Sleepiness Scale (ESS) is an 8 point questionnaire routinely used in patients with sleep and breathing disorders, and will be administered to measure the subject?s propensity to fall asleep during various routine daytime activities
Timepoint [4] 287544 0
one, three and 12 months
Secondary outcome [5] 287545 0
Differences between groups in physical activity following therapy.
a) Subjects will be asked to wear the SenseWear Pro3 Armband (SWA, Bodymedia, Pittsburgh, USA) for a seven day period (including weekend days) to document physical activity levels. This monitor is approved by the TGA (175835 Emergo Asia Pacific Pty Ltd - Patient data recorder, long-term, physical activity).
The monitor is worn over the upper part of the right arm and provides estimates of energy and step count. These estimates are made non-invasively using thin inbuilt bi-axial accelerometer, galvanic skin resistance plus sensors for heat flux, galvanic skin response and near-body ambient temperature. The number of non-sedentary minutes per day (energy expenditure >1.5METS) will be calculated.
Timepoint [5] 287545 0
Three months

Eligibility
Key inclusion criteria
Primary diagnosis of Obesity Hypoventilation Syndrome
Body mass index >30kg.m-2
Daytime respiratory failure with a PaCO2>45mmHg
At randomization, pH is in the normal range for chronic hypercapnia
FEV1/FVC ratio >70%
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Hypoventilation attributable to other causes eg neuromuscular disease, chest wall abnormalities, multiple medications with sedative/respiratory depressant side-effects
Physician diagnosed chronic obstructive pulmonary disease
Has used non-invasive ventilation (Bilevel PAP or CPAP) for more than one month in the previous 3 months.
Not proficient in English
Inability to provide informed consent

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)
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
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
NSW,VIC

Funding & Sponsors
Funding source category [1] 269628 0
Charities/Societies/Foundations
Name [1] 269628 0
ResMed Foundation
Address [1] 269628 0
PO Box 2448, San Diego, CA 92038, USA
Country [1] 269628 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
Institute for Breathing and Sleep
Address
Bowen Centre. Austin Health
PO Box 5555 Heidelberg
3084 Vic
Country
Australia
Secondary sponsor category [1] 266659 0
Charities/Societies/Foundations
Name [1] 266659 0
ResMed foundation
Address [1] 266659 0
PO Box 2448, San Diego, CA 92038, USA
Country [1] 266659 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269574 0
Austin Health Human Ethics Research Committee
Ethics committee address [1] 269574 0
Ethics committee country [1] 269574 0
Australia
Date submitted for ethics approval [1] 269574 0
01/08/2011
Approval date [1] 269574 0
06/10/2011
Ethics approval number [1] 269574 0

Summary
Brief summary
Not being able to breath enough overnight is a major problem for an increasing number of Australians with obesity.
Obesity hypoventilation syndrome, as this problem is known, is now the major reason for complex, overnight
breathing support in Australia. This potentially fatal disease can be managed using two different strategies; a
cheaper, simpler option available to more people or a more expensive approach that requires specialised services.
The more complex approach may not be better if fewer people are able to take advantage of it.
In this twelve month study, people with obesity hypoventilation syndrome will be randomised (like flipping a coin) to receive either the simple or the complex way of managing the disease. The primary question we are looking to answer is whether the more complex approach is really better than the simpler one. Specifically, the study will determine which treatment is better for patients in terms of quality of life, blood test results and and how easily they can get out and about. The study will also help establish which of these approaches is more cost-effective for the community.
Trial website
Trial related presentations / publications

Howard, M. E., A. J. Piper, B. Stevens, A. E. Holland, B. J. Yee, E. Dabscheck, D. Mortimer, A. T. Burge, D. Flunt, C. Buchan, L. Rautela, N. Sheers, D. Hillman and D. J. Berlowitz (2016). "A randomised controlled trial of CPAP versus non-invasive ventilation for initial treatment of obesity hypoventilation syndrome." Thorax.

Public notes

Contacts
Principal investigator
Name 32995 0
Prof David Hillman
Address 32995 0
Sir Charles Gairdner Hospital
1st Floor, G Block / Hospital Avenue,
Nedlands, WA 6009
Country 32995 0
Australia
Phone 32995 0
+61 8 9346 3011
Fax 32995 0
Email 32995 0
david.hillman@health.wa.gov.au
Contact person for public queries
Name 16242 0
Dr David Berlowitz
Address 16242 0
Institute for Breathing and Sleep
Bowen Centre. Austin Health
PO Box 5555
Heidelberg. 3084 Vic
Country 16242 0
Australia
Phone 16242 0
+61 3 9496 3871
Fax 16242 0
Email 16242 0
david.berlowitz@austin.org.au
Contact person for scientific queries
Name 7170 0
Dr David Berlowitz
Address 7170 0
Institute for Breathing and Sleep
Bowen Centre. Austin Health
PO Box 5555
Heidelberg. 3084 Vic
Country 7170 0
Australia
Phone 7170 0
+61 3 9496 3871
Fax 7170 0
Email 7170 0
david.berlowitz@austin.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary