ANZCTR - Registration

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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]

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

Condition category

Condition code

Respiratory

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]

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]

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]

Part A: First sleep study (on and off therapy)

Primary outcome [2]

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]

Second sleep study (nasal CPAP alone and in combination with MADopen and MADclosed)

Secondary outcome [1]

Part B: Epiglottic pressure (Pepi) swings during sleep (cmH2O) as assessed using a pressure transducer tipped catheter placed via the nares

Timepoint [1]

Second sleep study

Secondary outcome [2]

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]

Second sleep study

Secondary outcome [3]

Part A: awake nasal resistance (cmH2O/L/sec) as assessed by the measurement of nasal flow and choanal pressure

Timepoint [3]

Prior to commencement of first sleep study

Secondary outcome [4]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Neuroscience Research Australia (NeuRA) - Randwick

Recruitment postcode(s) [1]

2031 - Randwick

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Oventus Medical Ltd

Address [1]

1 Swann Road
Indooroopilly QLD 4068

Country [1]

Australia

Funding source category [2]

Other Collaborative groups

Name [2]

Cooperative Research Centre Project (CRC-P)

Address [2]

Commonwealth Government
Department of Industry, Innovation and Science
10 Binara St, Canberra ACT 2601

Country [2]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Oventus Medical Ltd

Address

1 Swann Road
Indooroopilly QLD 4068

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Other

Name [1]

Neuroscience Research Australia

Address [1]

Neuroscience Research Australia
Barker Street Randwick
Sydney NSW 2031

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Eastern Sydney Local Health District HREC

Ethics committee address [1]

Research Support Office
G71 East Wing, Edmund Blacket Building
Prince of Wales Hospital 
RANDWICK NSW 2031

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/11/2016

Approval date [1]

13/02/2017

Ethics approval number [1]

HREC/16-356 POWH/711

Summary

Brief summary

Up to 50% of OSA patients are unable to tolerate CPAP therapy leaving many OSA patients without treatment. Mandibular Advancement Devices are a suitable alternative for many patients however, as individual responses to MAD vary, combination therapies including CPAP-MAD are increasingly considered as an alternative therapeutic option and may result in lower pressure requirement and improve tolerance.

The present study aims to:
1.  evaluate MAD response as a function of nasal resistance and 
2. evaluate the impact of combination therapy on pressures required to stabilise the upper airway, in participants who are non-responders to MAD treatment alone.

Trial website

Trial related presentations / publications

1.	Lai V, Tong BK, Tran C, Ricciardiello A, Donegan M, Murray NP, Carberry JC, Eckert DJ. Combination Therapy with Mandibular Advancement and Expiratory Positive Airway Pressure (EPAP) Valves Reduces OSA Severity. Sleep 2019: Accepted 18 April.

2. Tong BK, Tran C, Ricciardiello A, Chiang A, Donegan M, Murray NP, Szollosi I, Amatoury J, Carberry JC, Eckert DJ. Efficacy of a Novel Oral Appliance and the Role of Posture on Nasal Resistance in Obstructive Sleep Apnea. J Clin Sleep Med 2019: Accepted 9 May.

Public notes

Contacts

Principal investigator

Name

A/Prof Danny J Eckert

Address

Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street Randwick Sydney NSW 2031

Country

Australia

Phone

+61 2 9399 1814

Fax

[email protected]

Contact person for public queries

Name

Danny J Eckert

Address

Neuroscience Research Australia Margarete Ainsworth Building Barker Street Randwick Sydney NSW 2031

Country

Australia

Phone

+61 2 9399 1814

Fax

[email protected]

Contact person for scientific queries

Name

Danny J Eckert

Address

Neuroscience Research Australia
Margarete Ainsworth Building
Barker Street Randwick Sydney NSW 2031

Country

Australia

Phone

+61 2 9399 1814

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
2098	Ethical 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

Source	Title	Year of Publication	DOI
Embase	Efficacy of a novel oral appliance and the role of posture on nasal resistance in obstructive sleep apnea.	2020	https://dx.doi.org/10.5664/jcsm.8244

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

Trial Review

Documents added manually

Documents added automatically