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Trial registered on ANZCTR


Registration number
ACTRN12617000492358
Ethics application status
Approved
Date submitted
28/03/2017
Date registered
5/04/2017
Date last updated
8/06/2022
Date data sharing statement initially provided
15/05/2019
Date results provided
8/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination therapy for obstructive sleep apnoea.
Scientific title
Targeted combination therapy with Mandibular Advancement Device (MAD) and Continuous Positive Airway Pressure (CPAP) : Physiological mechanistic studies to inform treatment for obstructive sleep apnoea (OSA)
Secondary ID [1] 291067 0
Sponsor ID: OVEN-005
Universal Trial Number (UTN)
U1111-1192-4586
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obstructive sleep apnoea 301864 0
Condition category
Condition code
Respiratory 301544 301544 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Oventus O2Vent T is a custom-made oral appliance or Mandibular Advancement Device (MAD), similar in appearance to a mouth guard designed to treat snoring and sleep apnoea. It is made up of two parts. The main structure which forms the breathing port at the front leading to the airways on each side to the rear of the appliance, is made from polished medical grade titanium with a polymer insert. The lower portion is made from dual laminate and is positioned in an advanced position to bring the jaw forward and adjusted using a screw titration mechanism.

The O2Vent T Mandibular Advancement Device (MAD) is delivered by a qualified dentist and worn every night during sleep and removed on waking. The acclimatization and treatment optimization period may vary from 1 week to several months. This involves getting used to wearing the device and establishing the optimum jaw position to balance comfort and resolution of symptoms as assessed by the Dentist fitting the device, Further advancement of the lower jaw is obtained using the screw titration mechanism in the O2Vent T. People fitted and acclimatised to this device for the treatment of OSA will be asked to participate in this study. There are no study related procedures prior to acclimatization and treatment optimization..

Part A
The study will involve a Level 1 in laboratory sleep study consisting of half night with and half the night without MAD in place, in order to assess efficacy based on the Apnoea-Hypopnoea Index (AHI) and to determine if the inclusion criteria for Part B is met. In addition to the standard clinical sleep study, nasal resistance will be evaluated. When the MAD is being worn, the device airway will remain open (MADopen) in this part of the study.

Part B
Participants who are deemed as non-responders to MAD based on a residual AHI > 10 events per hour sleep, will be asked to participate in Part B with a minimum of 1 week separating Part A and B. Part B study night will consist of another Level 1 in laboratory sleep study with additional measurements of pressures in the throat.

CPAP will be applied during this single night study in a research laboratory setting by investigators experienced in complex sleep studies and the application of CPAP, via an interface or mask. .CPAP will be applied alone and in combination with MAD with the device airway open and closed i.e. CPAP-MADopen and CPAP-MADclosed and titrated based on flow limitation and/or epiglottic pressure. Closing and opening the device airway is established using a connector that either allows for or blocks flow through the device airway. There is no washout period in between the administration of the treatments during this overnight investigation as the immediate physiological responses to treatment are of interest. If time permits, a fourth condition will be examined. CPAP will be applied via the device airway (CPAPdevice-MAD) with the device airway being open for the application of CPAP.

Part C
Participants who take part in Part B and those with a residual AHI on MAD >5 events/h will be asked to return for a Level 1 in laboratory sleep study consisting of half night with MAD+ an expiratory valve over the oral airway on the device and half the night with MAD+ expiratory valve over the oral airway on the device + the nose in order to assess efficacy of combination therapy (MAD+ expiratory valves) on the Apnoea-Hypopnoea Index (AHI).
Intervention code [1] 297055 0
Treatment: Devices
Comparator / control treatment
Part A: MAD will be compared to no treatment
Part B: optimal pressure with nasal CPAP alone will be compared to 1. CPAP-MADopen and 2. CPAP-MADclosed. In a subgroup of participants where time permits, CPAP will be applied directly via the device airway only.
Part C: MAD alone will be compared to MAD + oral and/or nasal expiratory valves
Control group
Active

Outcomes
Primary outcome [1] 300943 0
Part A: OSA severity as measured by AHI (number of apnoeas and hypopneas per hour of sleep) obtained from an overnight polysomnography (PSG)
Timepoint [1] 300943 0
Part A: First sleep study (on and off therapy)
Primary outcome [2] 301167 0
Part B: Positive pressure required to stabilize upper airway (cmH2O) obtained during the CPAP titration and informed by flow and epiglottic pressure recordings.
Timepoint [2] 301167 0
Second sleep study (nasal CPAP alone and in combination with MADopen and MADclosed)
Secondary outcome [1] 331252 0
Part B: Epiglottic pressure (Pepi) swings during sleep (cmH2O) as assessed using a pressure transducer tipped catheter placed via the nares
Timepoint [1] 331252 0
Second sleep study
Secondary outcome [2] 333223 0
Part B: OSA severity as measured by AHI (number of apnoeas and hypopneas per hour of sleep) obtained from an overnight polysomnography (PSG)
Timepoint [2] 333223 0
Second sleep study
Secondary outcome [3] 333328 0
Part A: awake nasal resistance (cmH2O/L/sec) as assessed by the measurement of nasal flow and choanal pressure
Timepoint [3] 333328 0
Prior to commencement of first sleep study
Secondary outcome [4] 343932 0
Part C: OSA severity as measured by AHI (number of apnoeas and hypopneas per hour of sleep) obtained from an overnight polysomnography (PSG)
Timepoint [4] 343932 0
Third sleep study

Eligibility
Key inclusion criteria
1. Otherwise healthy adult men and women with OSA
2. Currently using Oventus MAD as their primary treatment
3. Participants who are willing and able to give written informed consent and willingness to participate and comply with the study procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
2. Patients with any other medical condition which may interfere in the evaluation of the study.
3. People with intellectual or mental impairment or any condition that may interfere with their ability to consent for themselves.
4. Patients with a previous history of addiction to alcohol or drugs.
5. Patients taking medications known to affect sleep or pharyngeal muscle activity.
6. Previous side effects or known allergies to the sleeping pill zopiclone.

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 envelopes will be provided with the randomization sequence.
Analyses of sleep studies will be performed blinded to the treatment allocation.


Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation completed using an online randomisation generator (http://www.randomization.com/).

Participants in part A will undergo a split night sleep study half the night with i) no MAD in place (diagnostic only) and half the night with ii) O2Vent T Mandibular Advancement Device (MAD) in place. The order of MAD and no MAD will be randomized 1:1 using random permuted blocks with random block sizes.

Part B is a three-way cross-over study with participants receiving i) CPAP nasal ii) CPAP–MAD open and iii) CPAP-MAD closed. CPAP nasal will be randomised as either the 1st or third treatment in each randomisation. If time permits participants will receive a fourth treatment iv) CPAPdevice–MAD which will be allocated as the final treatment in each case. Randomisation will therefore be 1:1:1:1 between ABC, ACB, BCA, CBA

Participants in part C will undergo a split night sleep study half the night with i) MAD+ Expiratory oral valve in place and half the night with ii) MAD+ Expiratory oral and nasal valve in place. The order will be randomized 1:1 using random permuted blocks with random block sizes.
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 primary outcome for Part B will be to compare the CPAP level required to normalise the AHI with and without MAD, according to the gold standard airflow-epiglottic pressure swing profile.
Prior data indicate that the difference in the response of matched pairs is normally distributed with a standard deviation 2.3cmH2O. If the true difference in the mean response of matched pairs is 1.8 cmH2O, we will need to study 15 participants to be able to reject the null hypothesis that the difference is zero with probability (power) of >0.8 (paired t-test). The Type I error probability associated with this test of this null hypothesis is 0.05. Accordingly, given that approximately one third of patients with OSA fitted with MAD do not yield a reduction in AHI<10 events/h (“non-responder”), we anticipate that we will need to recruit approximately 45 participants for Part A to yield complete data for n=15 in Part B. The number recruited for Part A will be adjusted as necessary to yield sufficient data according to actual responder rates. For Part A, only participants who are recommended oral appliance therapy by their treating physician and are prospectively recruited into the study will be included for the primary efficacy outcome analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/04/2017
Actual
6/04/2017
Date of last participant enrolment
Anticipated
Actual
9/08/2018
Date of last data collection
Anticipated
Actual
10/08/2018
Sample size
Target
45
Accrual to date
Final
47
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7433 0
Neuroscience Research Australia (NeuRA) - Randwick
Recruitment postcode(s) [1] 15239 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 295506 0
Commercial sector/Industry
Name [1] 295506 0
Oventus Medical Ltd
Country [1] 295506 0
Australia
Funding source category [2] 302789 0
Other Collaborative groups
Name [2] 302789 0
Cooperative Research Centre Project (CRC-P)
Country [2] 302789 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Oventus Medical Ltd
Address
1 Swann Road
Indooroopilly QLD 4068
Country
Australia
Secondary sponsor category [1] 294327 0
None
Name [1] 294327 0
Address [1] 294327 0
Country [1] 294327 0
Other collaborator category [1] 279416 0
Other
Name [1] 279416 0
Neuroscience Research Australia
Address [1] 279416 0
Neuroscience Research Australia
Barker Street Randwick
Sydney NSW 2031
Country [1] 279416 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296834 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 296834 0
Ethics committee country [1] 296834 0
Australia
Date submitted for ethics approval [1] 296834 0
28/11/2016
Approval date [1] 296834 0
13/02/2017
Ethics approval number [1] 296834 0
HREC/16-356 POWH/711

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

Contacts
Principal investigator
Name 72174 0
A/Prof Danny J Eckert
Address 72174 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street Randwick Sydney NSW 2031

Country 72174 0
Australia
Phone 72174 0
+61 2 9399 1814
Fax 72174 0
Email 72174 0
d.eckert@neura.edu.au
Contact person for public queries
Name 72175 0
Danny J Eckert
Address 72175 0
Neuroscience Research Australia Margarete Ainsworth Building Barker Street Randwick Sydney NSW 2031
Country 72175 0
Australia
Phone 72175 0
+61 2 9399 1814
Fax 72175 0
Email 72175 0
d.eckert@neura.edu.au
Contact person for scientific queries
Name 72176 0
Danny J Eckert
Address 72176 0
Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street Randwick Sydney NSW 2031
Country 72176 0
Australia
Phone 72176 0
+61 2 9399 1814
Fax 72176 0
Email 72176 0
d.eckert@neura.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This was not requested at the time of original ethical approval.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2098Ethical approval    372279-(Uploaded-15-05-2019-10-56-36)-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
SourceTitleYear of PublicationDOI
EmbaseEfficacy of a novel oral appliance and the role of posture on nasal resistance in obstructive sleep apnea.2020https://dx.doi.org/10.5664/jcsm.8244
N.B. These documents automatically identified may not have been verified by the study sponsor.