Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001081202
Ethics application status
Approved
Date submitted
3/04/2018
Date registered
28/06/2018
Date last updated
23/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Mandibular Advancement Splint treatment for Sleep Apnoea in patients with Atrial Fibrillation.
Scientific title
A pilot study of patient acceptance, compliance and efficacy of Mandibular Advancement Splint therapy for the treatment of Obstructive Sleep Apnoea in a hospital cohort with Atrial Fibrillation.
Secondary ID [1] 294485 0
None
Universal Trial Number (UTN)
U1111-1211-6664
Trial acronym
MANTA
Linked study record
This study is a sub-study of the approved trial ACTRN12616001016426.

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 307252 0
Obstructive Sleep Apnoea 307253 0
Condition category
Condition code
Cardiovascular 306370 306370 0 0
Other cardiovascular diseases
Respiratory 306371 306371 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The exposure in this trial is a Mandibular Advancement Splint (MAS) for the treatment of Obstructive Sleep Apnoea.
MAS is an oral appliance device which adheres to the top and bottom dental arches and advances the mandible in relation to the maxilla.
The device will be manufactured for individual patients in the trial by a specialist dentist.
Study visits relating to the device are as follows:
Visit 1: Dental impressions taken
Visit 2 (4 weeks after visit 1): MAS splint fitting, titration, education. Ideally timed to occur prior to the patient's planned PVI, if relevant. Once Visit 2 has occurred, the treatment phase of the trial commences.
Visit 3 (8 - 12 weeks after visit 1): MAS treatment review. Following the MAS treatment review, patients will wear the device over the trial period of 12 months.
Regular trial assessments will take place at 3, 6 and 12 months following the start of the treatment phase.
The efficacy of the device (improvement in the patient's sleep apnoea whilst wearing the device) will be assessed at 6 months with a repeat diagnostic sleep study. This will be compared to the patients' pre-treatment sleep study.
Compliance will be assessed as average hours of nightly use as recorded by the inbuilt dentirac compliance recorder.
Patient acceptance will be measured as the proportion of patients who continue to use MAS at the various timepoints (3, 6 and 12 months), as well as via MAS subjective assessment questionnaires.
Intervention code [1] 300782 0
Treatment: Devices
Comparator / control treatment
MAS "responders" will be compared to the "non-responder" group.
A "responder" is defined as a patient who has an improvement in their AHI (apnoea hypopnea index) on MAS therapy.
This could be a complete or partial response.
Complete response = AHI less than or equal to 10
Partial response = AHI greater than 10 but reduced by 50% from original AHI.
A non-responder fails to meet the above criteria for a responder.
Control group
Active

Outcomes
Primary outcome [1] 305381 0
Patient acceptance of the device. This will be assessed by the proportion of patients who continue to wear the device at the various timepoints (3, 6 and 12 months post commencement of the treatment phase). This will be patient reported and confirmed via the inbuilt compliance recorder
Timepoint [1] 305381 0
3, 6 and 12 months following commencement of the treatment phase.
Primary outcome [2] 305382 0
Efficacy of the device as measured by the change in AHI with the device in situ. The AHI (apnoea hypopnea index) is a measure of sleep apnoea severity and is defined as the number of sleep apnoea events which occur on average per hour of sleep, as measured by the current American Academy of Sleep Medicine (AASM) guidelines. This is determined by a diagnostic sleep study at 6 months post commencement of the treatment phase which is compared to the pre-treatment diagnostic sleep study.
Timepoint [2] 305382 0
6 months post commencement of the treatment phase.
Primary outcome [3] 305383 0
Device compliance as recorded by inbuilt "dentitrac" compliance recording device, measured as average nightly hours of device use.
Timepoint [3] 305383 0
3, 6 and 12 months post commencement of the treatment phase.
Secondary outcome [1] 345020 0
AF burden as a composite of: 1. Holter monitor at 3, 6 and 12 months post commencement of the treatment phase. 2. AliveCor Kardia "app" (smartphone device) daily ECG recording. 3. Clinical notes review at 3, 6, 12 months post commencement of the treatment phase. 4. Patient interview at 3, 6, 12 months post commencement of the treatment phase. 5. Patient AF symptom diary
Timepoint [1] 345020 0
3, 6 and 12 months post commencement of the treatment phase.
Secondary outcome [2] 345021 0
Change in quality of life score: AFEQT
Timepoint [2] 345021 0
3, 6 and 12 months post commencement of the treatment phase.
Secondary outcome [3] 345022 0
Heart Rate Variability (HRV) will be assessed and compared using Electrocardiogram (ECG) data from both the baseline PSG (polysomnogram) prior to treatment commencement and the progress PSG on treatment at 6 months.
Parameters of HRV will be analysed from a short period of restful wake (eg 3 - 5 minutes) at the beginning of the study. Both time-domain and frequency-domain parameters will be assessed using the Kubios software program. These are as follows:
Time Domain:
1. The mean of ECG RR intervals
2. Standard deviation of RR intervals
3. The mean heart rate
4. Standard deviation of instantaneous heart rate values
5. Square root of the mean squared differences between successive RR intervals
6. Number of successive RR interval pairs that differ more than 50 ms (NN50)
7. NN50 divided by the total number of RR intervals
8. The integral of the RR interval histogram divided by the height of the histogram
9. Baseline width of the RR interval histogram

Frequency-Domain
1. Very low frequency (VLF), low frequency (LF) and high frequency (HF) peaks
2. VLF, LF and HF powers (absolute and relative)
3. Ratio between LF and HF band powers
4. Total spectral power
5. ECG derived respiratory frequency

Further information on methodology can be found at:
Tarvainen, M. P., J. P. Niskanen, J. A. Lipponen, P. O. Ranta-Aho and P. A. Karjalainen (2014). "Kubios HRV--heart rate variability analysis software." Comput Methods Programs Biomed 113(1): 210-220.
Timepoint [3] 345022 0
3, 6, 12 months post commencement of the treatment phase.
Secondary outcome [4] 345023 0
Change in atrial size as measured by echocardiography
Timepoint [4] 345023 0
12 months post commencement of the treatment phase.
Secondary outcome [5] 345024 0
Change in 24 hour blood pressure as measured via 24 hour ambulatory BP recording.
Timepoint [5] 345024 0
3, 6 and 12 months post commencement of the treatment phase.
Secondary outcome [6] 348594 0
MAS subjective assessment questionnaire to assess patient subjective experience on MAS treatment. This short questionnaire was developed specifically for this study and addresses questions of patient comfort, subjective assessment of MAS efficacy and satisfaction with the device.
Timepoint [6] 348594 0
3, 6 and 12 months post commencement of the treatment phase
Secondary outcome [7] 348595 0
Change in quality of life score: SF-36
Timepoint [7] 348595 0
3, 6 and 12 months post commencement of the treatment phase
Secondary outcome [8] 348596 0
Change in quality of life score: FOSQ-10
Timepoint [8] 348596 0
3, 6 and 12 months post commencement of the treatment phase

Eligibility
Key inclusion criteria
1. Completion of parent study with > or equal to 2 episodes of AF in the last 12 months.
2. Sleep Apnoea present: Apnoea Hypopnea index (AHI) > 10
3. Anatomically suitable for Mandibular Advancement Splint (MAS) eg sufficient number of native teeth as assessed by specialist dentist
4. Patient consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Anatomically unsuitable for MAS (eg insufficient native teeth).
2. Not physically able to complete the trial: eg geriatric issues including reduced mobility, frailty, frequent falls, need for carer
3. Life expectancy less than 12 months as judged by the study physician
4. Significant active comorbidities which may impair the patient's ability to complete the trial, including but not limited to severe cardiovascular disease, active malignancy, end-stage renal failure, hospital inpatient
5. Psychiatric/mental health conditions which may impair the ability to complete the trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
n/a
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
n/a
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcomes will be analysed as follows:
1. Patient acceptance: the proportion of patients who continue to use their MAS device at intervals of 3, 6 and 12 months.
2. Compliance: the average number of hours per night that the MAS is used by the patient as assessed by the in-built denti-trac chip at 3, 6 and 12 months
3. Efficacy: the change in AHI on in-laboratory sleep study with the device in-situ at 6 months when compared with baseline.
Secondary characteristics as described will be compared between MAS "resonders" and "non-responders" using mean ± standard deviation or as proportions (percentages). A p value of < 0.05 will be considered statistically significant.
Sample size:
As this is a pilot study to assess the treatment of MAS therapy in this patient group, there is a small sample size of 20 patients.
Data arising from this study can be used to inform power calculations for a larger, randomised control trial.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2018
Actual
Date of last participant enrolment
Anticipated
1/03/2019
Actual
Date of last data collection
Anticipated
2/03/2020
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10533 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 10534 0
North Shore Private Hospital - St Leonards
Recruitment postcode(s) [1] 22253 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 299111 0
Hospital
Name [1] 299111 0
Department of Respiratory and Sleep Medicine, Royal North Shore Hospital
Country [1] 299111 0
Australia
Funding source category [2] 299903 0
University
Name [2] 299903 0
Charles Perkins Centre, the University of Sydney
Country [2] 299903 0
Australia
Primary sponsor type
Hospital
Name
Department of Respiratory and Sleep Medicine, Royal North Shore Hospital.
Address
Level 8
Pacific Highway
St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 298368 0
University
Name [1] 298368 0
University of Sydney
Address [1] 298368 0
Camperdown NSW 2006
Country [1] 298368 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300043 0
'Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300043 0
Ethics committee country [1] 300043 0
Australia
Date submitted for ethics approval [1] 300043 0
17/10/2017
Approval date [1] 300043 0
16/02/2018
Ethics approval number [1] 300043 0
HREC/16/HAWKE/25, RESP/16/16

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

Contacts
Principal investigator
Name 82370 0
Dr Anna Mohammadieh
Address 82370 0
Dept of Respiratory and Sleep Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards NSW 2065
Country 82370 0
Australia
Phone 82370 0
+612 9463 2925
Fax 82370 0
Email 82370 0
[email protected]
Contact person for public queries
Name 82371 0
Anna Mohammadieh
Address 82371 0
Dept of Respiratory and Sleep Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards NSW 2065
Country 82371 0
Australia
Phone 82371 0
+612 9463 2925
Fax 82371 0
Email 82371 0
[email protected]
Contact person for scientific queries
Name 82372 0
Anna Mohammadieh
Address 82372 0
Dept of Respiratory and Sleep Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards NSW 2065
Country 82372 0
Australia
Phone 82372 0
+612 9463 2925
Fax 82372 0
Email 82372 0
[email protected]

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

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