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Trial registered on ANZCTR

Registration number

ACTRN12615000918527

Ethics application status

Approved

Date submitted

20/07/2015

Date registered

2/09/2015

Date last updated

19/10/2016

Type of registration

Retrospectively registered

Titles & IDs

Public title

Cooperative Research Centre (CRC) for Alertness, Safety and Productivity: Respiratory Phenotyping for Obstructive Sleep Apnoea – Main study

Scientific title

Detailed analysis of the underlying respiratory causes of Obstructive Sleep Apnoea and assessment of the efficacy of oxygen as a treatment option.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Obstructive Sleep Apnoea

Condition category

Condition code

Respiratory

Sleep apnoea

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Step 1: Simple OSA respiratory phenotyping via CPAP drops during CPAP titration (this step aims to recruit a total of 300 participants)

Following diagnosis, screening and consent each patient will undergo a single night modified CPAP titration study. The modified CPAP titration study will be administered by research staff, as part of normal care in the sleep laboratory, in order to establish an appropriate CPAP treatment pressure and establish airflow responses to experimental CPAP pressure drops to zero pressure. The modified CPAP titration study is very similar to a routine CPAP titration study. The only difference being the addition of a calibrated airflow sensor measurements and around 5 very brief drops in pressure of the CPAP machine during the night. The averaged airflow responses to these experimental CPAP pressure drops to zero will be used to categorise participants into one of three groups;

a) “good airway” (average peak inspiratory airflow >50% of baseline preceding pressure drops)
b) “intermediate airway” (30-50%)
c) “poor airway” (<30%)

All “good airway” and “intermediate airway” patients and approximately 1 in 4 of the remaining “poor airway” participants chosen at random will be selected for inclusion in Step 2 and 3 of the protocol.

Step 2: Detailed OSA respiratory phenotyping study (this step aims to recruit a total of 120 participants).

All patients will undergo a 1 night detailed in-laboratory sleep and respiratory physiology study using the method described by Wellman et al. (J Appl Physiol., 114(7), 911-22, 2013). This method uses a combination of systematic gradual and rapid CPAP drops and rapid returns to therapeutic pressure to characterise all of the major known pathophysiological deficits and respiratory phenotypes underlying OSA.

As in step 1, patients will be instrumented for a conventional full diagnostic sleep study and wear a snug fitting CPAP mask fitted with a calibrated pneumotachograph to quantify airflow.

Additional secondary measures in sub-groups of patients will be conducted to characterise wake respiratory control. These secondary measures involve a short period of quiet breathing on room air and then breathing from either room air or a gas with increased carbon dioxide levels using a computer controlled system that characterizes the responsiveness of the main carbon dioxide sensitive reflexes that control breathing. The levels of carbon dioxide are similar to the levels normally breathed out and well below those considered unsafe. These measures are conducted prior to bedtime on the night of the in-laboratory sleep study and will be repeated with and without a background of increased O2 levels to investigate the change in CO2 sensitivity when patients are treated with oxygen.

Step 3: Acute 1 night O2 versus 1 night air study (this step aims to recruit all 120 participants from Step 2).

This step will identify patients who can be effectively treated with O2.

All patients will undergo 2 separate in-laboratory sleep study nights, one on O2 therapy the other on air (control) in random order (via minimisation to help achieve balance in key potential confounders, such as gender, age and BMI, between treatment allocation orders) approximately 1 week apart, with patients and sleep study scorers blinded to treatment allocation.

As in step 1 participants will be instrumented for a conventional full diagnostic sleep study but without a mask. Participants will wear 2 nasal cannulae; one for conventional nasal pressure recordings, the other for delivery of O2 or medical air at 4 l/min.

Each step (1-3) will be conducted approximately 1 week apart.

Intervention code [1]

Treatment: Other

Comparator / control treatment

Active. All patients will undergo 2 separate in-laboratory sleep study nights one on O2 therapy the other on air (control) in random order (via minimisation to help achieve balance in key potential confounders, such as gender, age and BMI, between treatment allocation orders) approximately 1 week apart

Control group

Active

Outcomes

Primary outcome [1]

Apnoea-Hypopnoea Index (AHI) scored without conventional oxygen desaturation criteria

Timepoint [1]

AHI assessed without standard desaturation criteria will be measured from each overnight polysomnography study (baseline night, single night of O2 treatment alone, single night of air (control) treatment) and compared between nights.

Secondary outcome [1]

3% Oxygen desaturation index assessed using pulse oximetry

Timepoint [1]

3% Oxygen desaturation index will be measured from each overnight polysomnography study (baseline night, single night of O2 treatment alone, single night of air (control) treatment) and compared between nights.

Secondary outcome [2]

Minimum oxygen saturation assessed using pulse oximetry

Timepoint [2]

Minimum oxygen saturation will be measured from each overnight polysomnography study (baseline night, single night of O2 treatment alone, single night of air (control) treatment) and compared between nights.

Secondary outcome [3]

Respiratory event duration assessed using polysomnography

Timepoint [3]

Respiratory event duration will be measured from each overnight polysomnography study (baseline night, single night of O2 treatment alone, single night of air (control) treatment) and compared between nights.

Secondary outcome [4]

Arousal frequency assessed using polysomnography

Timepoint [4]

Arousal frequency will be measured from each overnight polysomnography study (baseline night, single night of O2 treatment alone, single night of air (control) treatment) and compared between nights.

Eligibility

Key inclusion criteria

- Diagnosis of obstructive sleep apnea
- Recommended usual care with CPAP treatment by their treating physician

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- A history of significant COPD (Gold criteria 3-4), chronic ventilatory failure from any other cause or psychiatric disorders likely to place the patient at higher than normal risk or likely to confound experimental treatment outcomes.
- Physician recommended exclusion
- Patient unable (e.g. language difficulties) or unwilling to consent
- Central sleep apnea (central apnea index >5 /hr)

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

Recruiting

Date of first participant enrolment

Anticipated

9/04/2015

Actual

9/04/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

300

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Cooperative Research Centre (CRC) for Alertness, Safety, and Productivity

Address [1]

Alertness CRC Ltd
Monash University
Ground Floor BASE Facility
264 Ferntree Gully Road
Notting Hill
VIC, 3468

Country [1]

Australia

Primary sponsor type

Individual

Name

A/Prof Peter Catcheside

Address

Sleep and Respiratory Medicine
Repatriation General Hospital
Daws Road
Daw Park
South Australia, 5041

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee (SACHREC)

Ethics committee address [1]

Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia, 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/11/2014

Approval date [1]

22/01/2015

Ethics approval number [1]

491.14 - HREC/14/SAC/516

Summary

Brief summary

Background: Obstructive sleep apnea (OSA) reflects variable overlap of several quite different causal mechanisms. Some patients have obesity-related upper airway narrowing as the major cause, while for others intrinsic respiratory control abnormalities, ineffective upper airway muscle responses and interactions with arousal appear to play the major role. CPAP, the gold standard treatment for OSA, effectively overcomes upper airway anatomical deficiency. It is effective in patients who successfully use it but is burdensome and long term adherence remains poor. Thus, more appropriate treatment strategies are urgently needed for OSA. This will require strategic change to current diagnostic and treatment practices to achieve optimal long-term treatment outcomes. To succeed, this approach requires clinically validated practical methods to identify respiratory phenotypes, followed by personally-tailored treatment to best target the patient’s particular underlying causal factors using CPAP or alternatives as indicated by phenotype testing.

The study aims to demonstrate the clinical utility of respiratory phenotyping for achieving improved treatment outcomes compared to current best-practice care. This main study will identify patients with unstable respiratory control who are most likely to benefit from O2 treatment, and more complex phenotypes who may benefit from alternative or combination treatments. Patients with a favourable single night O2 treatment response will be enrolled into a proof-of-concept multicentre, randomised controlled cross-over trial of 1 month of oxygen versus 1 month of CPAP (control) treatment to examine 1 month treatment outcomes (ACTRN12615000069550). Patients with a partial response to O2 and who demonstrate excessive awakening responses will be invited to participate in a pilot study of O2 plus sedative combination treatment (ACTRN12615000858594).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Peter Catcheside

Address

Sleep and Respiratory Medicine
Repatriation General Hospital
Daws Road
Daw Park
South Australia, 5041

Country

Australia

Phone

+61 8 8275 1187

Fax

peter.catcheside@health.sa.gov.au

Contact person for public queries

Name

Peter Catcheside

Address

Sleep and Respiratory Medicine
Repatriation General Hospital
Daws Road
Daw Park
South Australia, 5041

Country

Australia

Phone

+61 8 8275 1187

Fax

peter.catcheside@health.sa.gov.au

Contact person for scientific queries

Name

Peter Catcheside

Address

Sleep and Respiratory Medicine
Repatriation General Hospital
Daws Road
Daw Park
South Australia, 5041

Country

Australia

Phone

+61 8 8275 1187

Fax

peter.catcheside@health.sa.gov.au

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Dimensions AI	An assessment of a simple clinical technique to estimate pharyngeal collapsibility in people with obstructive sleep apnea	2020	https://doi.org/10.1093/sleep/zsaa067

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically