Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000050954
Ethics application status
Approved
Date submitted
13/12/2019
Date registered
22/01/2020
Date last updated
29/08/2024
Date data sharing statement initially provided
22/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimizing Obstructive Sleep Apnea Therapy in Patients with Acute Coronary Syndrome: A Pilot Randomised Control Trial
Scientific title
Impact of optimized Obstructive Sleep Apnea Therapy in Patients with Acute Coronary Syndrome: A Pilot Randomised Control Trial
Secondary ID [1] 300123 0
Nil
Universal Trial Number (UTN)
U1111-1245-1607
Trial acronym
SPACE_TRIALSPACE Intervention
Linked study record
Linked study will no longer be the recruitment pathway:
Our established prevalence study (SPACE study, No X18-0173 & HREC/18/RPAH/242) previously provided the recruitment pathway for this pilot RCT. Participants completing the prevalence study who met the criteria were invited to take part in this pilot trial.
This SPACE prevalence study has ended recruitment. Patient screening now directly for the SPACE Intervention trial

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 315555 0
Obstructive Sleep Apnea 315556 0
Condition category
Condition code
Cardiovascular 313847 313847 0 0
Coronary heart disease
Respiratory 313848 313848 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enrolled patients will be randomised into either the personalised obstructive sleep apnea (OSA) treatment group or usual medical care. The patients randomised into the personalised OSA treatment group will select either continuous positive airway pressure (CPAP) therapy or oral appliance therapy (OAT) based on physician recommendations and personal preference.

ARM 1: Personalised OSA treatment group, (CPAP or OAT)

CPAP therapy:
CPAP therapy will be overseen by an experienced sleep therapist over the intervention period of six-months. The sleep therapist will provide detailed CPAP therapy education to the patient during the first CPAP initiation visit (face to face). Patients are allowed to acclimatise to CPAP therapy over a period of approximately 8 weeks. This may include monthly phone calls and face to face visits as required. CPAP device settings may be adjusted in accordance with the patient’s feedback to optimize CPAP compliance and use. The intervention period begins when the patient is determined to be acclimatised to CPAP therapy (apnoea-hypopnea index <15 events/h and usage >5 hours per night). Patients who fail to meet this criterion will be offered oral appliance therapy or combination therapy.
Ongoing remote support will be maintained during the six-month intervention period. Remote monitoring of CPAP therapy usage will be conducted on a cloud-based patient management system. Patient engagement tools (ie. cloud-based mobile application) will be used to allow patients to receive feedback on their CPAP use during the intervention period.

Oral appliance therapy:
A custom-made oral appliance will be delivered by an experience dentist. Patients will undergo an oral health assessment with the dentist to determine suitability for oral appliance therapy. Patients not eligible for an oral appliance will be offered CPAP therapy. Patients are allowed to acclimatise to oral appliance therapy for approximately eight weeks. This involves establishing the optimum jaw position for comfort and resolution of OSA symptoms as assessed by the study dentist. The intervention period begins when the patient is determined to be acclimatised to oral appliance therapy (apnoea-hypopnea index <15 events/h and usage >5 hours per night). Patients who fail to meet this criterion will be offered CPAP therapy or combination therapy.
Patients on oral appliance therapy will be asked to complete an online sleep diary daily for remote monitoring of therapy. Ongoing remote support will be maintained during the six-month intervention period.

ARM 2: Usual care
This will represent a control group receiving conventional medical care by their cardiologist and primary care physician.
Intervention code [1] 316349 0
Treatment: Devices
Comparator / control treatment
The comparator will be the Usual care arm: This will represent a control group receiving conventional medical care by their cardiologist and primary care physician. Participants randomized into this group will not be given a device treatment for OSA. Furthermore comparison will also be made between the two different OSA treatments.

Conventional medical care will be any medical care prescribed by the participants cardiologist or primary care physician.
Control group
Active

Outcomes
Primary outcome [1] 322295 0
Daily usage data (mean hours used per day) of OSA therapy will be collected from a cloud based patient management system and patient diary.
Timepoint [1] 322295 0
At 6 months after commencement of intervention period.
Secondary outcome [1] 377993 0
24 hour ambulatory blood pressure and central blood pressure will be assessed using the automatic Sphygmocor.
Timepoint [1] 377993 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [2] 377994 0
Home sleep testing (polysomnography): composite changes in oxygen desaturation index (ODI), A metric used to define the presence and severity of OSA and to measure rapid eye movement OSA, which has specific association with cardiovascular risk.
Timepoint [2] 377994 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [3] 377997 0
Subjective measure of low and high risk of sleep disordered breathing will be assessed using the Berlin Questionnaire.
Timepoint [3] 377997 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [4] 378000 0
A subjective measure of quality of life will be assessed using the 36-Item short form survey.
Timepoint [4] 378000 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [5] 378001 0
Pulse oximetry: pulse oximetry is a non-invasive method for monitoring a person’s oxygen saturation.
Timepoint [5] 378001 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [6] 378002 0
Inflammation, assessed by composite outcome of of high-sensitivity C-reactive protein (hs-CRP) and Tumour Necrosis Factor Alpha (TNF-a) from venous blood.
Timepoint [6] 378002 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [7] 378005 0
Pulse wave velocity: The SphygmoCor XCEL system enables the non-invasive measurement of pulse wave velocity of the blood pressure waveform travelling between two arterial sites.
Timepoint [7] 378005 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [8] 378006 0
Autonomic function: measures of heart rate variability via 5 minute 2-lead ECG recording.
Timepoint [8] 378006 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [9] 378008 0
Cardiovascular Risk Factors: Composite outcome of blood lipids (triglycerides, LDL-C, HDL-C) and glycated haemoglobin (HbA1c) quantified by venous sampling. Body mass and height will be measured to determine body mass index using digital scales and measuring tape. Waist circumference will be measured according to standardised methods using a measuring tape.
Timepoint [9] 378008 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [10] 378168 0
Epworth Sleepiness Scale
Timepoint [10] 378168 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [11] 378169 0
A subjective measure of risk of obstructive sleep apnea will be assessed using the STOP-BANG questionnaire.

Timepoint [11] 378169 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [12] 378171 0
Seattle angina questionnaire
Timepoint [12] 378171 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [13] 439223 0
Diet quality tool (DQT) questionnaire
Timepoint [13] 439223 0
Secondary outcome [14] 439224 0
Diet quality tool (DQT) questionnaire
Timepoint [14] 439224 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [15] 439225 0
International Physical Activity Questionnaire (IPAQ)
Timepoint [15] 439225 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [16] 439226 0
International Physical Activity Questionnaire (IPAQ)
Timepoint [16] 439226 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [17] 439227 0
Food frequency questionnaire (FFQ)
Timepoint [17] 439227 0
Baseline and 6 months post commencement of intervention.
Secondary outcome [18] 439228 0
Food frequency questionnaire (FFQ)
Timepoint [18] 439228 0
Baseline and 6 months post commencement of intervention.

Eligibility
Key inclusion criteria
1. Patients with a recent (within 12 months of diagnosis) presentation of acute coronary syndrome (unstable angina, ST elevated myocardial infarction (EMI), non-STEMI).
2. Patients diagnosed with moderate to severe obstructive sleep apnoea with significant hypoxia defined as an Oxygen Saturation Index 3% (ODI 3%) > 10 events/hour on polysomnogram.
3. Clinically suitable for PAP and/or OAT treatment.
4. Willingness to undergo either PAP, OAT or usual care for 6 months.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous treatment for obstructive sleep apnea.
2. Contraindications to CPAP (severe nasal obstruction) or oral appliance therapy (insufficient teeth or dental health issues).
3. Women who are lactating or pregnant
4. Driving risk, report an accident (or near miss accident) because of sleepiness in the last 6 months
5. Need for immediate therapy as assessed by treating sleep physician.
6. Patients with a history of psychological illness or conditions such as to interfere with the patients ability to understand the requirements of the study
7. Coexisting sleep disorder, shift work, regular use of sedatives or narcotics, pre-existing lung disease (moderate to severe chronic obstructive pulmonary disease) or psychiatric disease; chronic kidney disease (eGFR<60).
8. Central sleep apnea (defined as >20% of respiratory events being central events, rather than obstructive events)

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)
The allocation sequence for the trial is set up using centralised randomization to maintain allocation concealment.
The allocation sequence was set by our data manager on RedCap and no other person in our trial has access to the allocation sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be done using a online random number generator tool to receive either Treatment or Usual care.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot randomised trial which will enable effect sizes for outcome measures following intervention to be calculated to inform future clinical trials. Therefore, a formal sample size calculation is not possible. We have adopted a sample size of 40:20 participants per arm. According to an exploration of pilot trial sample sizes values of a pilot trial, a sample size of 35 is theoretically optimal to detect a small effect size while using a conservative approach to estimating standard deviation (using at least 80% upper one-side confidence limit, rather than the estimate itself) to enable sample size calculation for a 90% powered main trial.

Descriptive statistics will be used to present information about therapy acceptance and usage in the sample. Differences between trial arms will be compared using ANOVA. Changes in surrogate cardiovascular measures across the treatment period and between trial arms will be assessed using factorial ANOVA. Calculated effectiveness metrics will be assessed for relationship to changes in outcome variables using correlation and regression analyses.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/02/2020
Actual
18/09/2020
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
60
Accrual to date
42
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15500 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 27047 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 28855 0
2050 - Camperdown
Recruitment postcode(s) [2] 43116 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 304018 0
Charities/Societies/Foundations
Name [1] 304018 0
Resmed Foundation Clinical Grant
Country [1] 304018 0
United States of America
Primary sponsor type
University
Name
University of Sydney
Address
Administration Building (F23)
Corner of Eastern Avenue and City Road,
The University of Sydney,
Camperdown
NSW
2006
Country
Australia
Secondary sponsor category [1] 304193 0
None
Name [1] 304193 0
Address [1] 304193 0
Country [1] 304193 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304510 0
Human Research Ethics Committee - Sydney Local health District, Royal Prince Alfred Hospital
Ethics committee address [1] 304510 0
Ethics committee country [1] 304510 0
Australia
Date submitted for ethics approval [1] 304510 0
12/06/2019
Approval date [1] 304510 0
15/08/2019
Ethics approval number [1] 304510 0

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

Contacts
Principal investigator
Name 97202 0
Prof Peter Cistulli
Address 97202 0
Department of Respiratory and Sleep Medicine
Royal North Shore Hospital
North Foyer Consulting Suites, Ground Floor,
North Shore Private Hospital,
Westbourne Street,
St Leonards NSW 2065
Country 97202 0
Australia
Phone 97202 0
+61 2 9463 2934
Fax 97202 0
Email 97202 0
peter.cistulli@sydney.edu.au
Contact person for public queries
Name 97203 0
Peter Cistulli
Address 97203 0
Department of Respiratory and Sleep Medicine
Royal North Shore Hospital
North Foyer Consulting Suites, Ground Floor,
North Shore Private Hospital,
Westbourne Street,
St Leonards NSW 2065
Country 97203 0
Australia
Phone 97203 0
+61 2 9463 2934
Fax 97203 0
Email 97203 0
peter.cistulli@sydney.edu.au
Contact person for scientific queries
Name 97204 0
Peter Cistulli
Address 97204 0
Department of Respiratory and Sleep Medicine
Royal North Shore Hospital
North Foyer Consulting Suites, Ground Floor,
North Shore Private Hospital,
Westbourne Street,
St Leonards NSW 2065
Country 97204 0
Australia
Phone 97204 0
+61 2 9463 2934
Fax 97204 0
Email 97204 0
peter.cistulli@sydney.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


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
No additional documents have been identified.