Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001328268p
Ethics application status
Not yet submitted
Date submitted
29/06/2018
Date registered
7/08/2018
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to evaLuate the Effect of trEating obstructive sleeP apnoea on coronary atherosclerosis with Computed Tomography (SLEEP-CT)
Scientific title
Study to evaLuate the Effect of trEating obstructive sleeP apnoea on coronary atherosclerosis with Computed Tomography
Secondary ID [1] 295320 0
None
Universal Trial Number (UTN)
Trial acronym
SLEEP-CT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
athersclerosis 308532 0
sleep apnoea 308533 0
Condition category
Condition code
Cardiovascular 307501 307501 0 0
Coronary heart disease
Respiratory 307502 307502 0 0
Sleep apnoea

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with moderate to severe (bases on a clinically indicated PSG) OSA will participate in this study as defined as either

AHI >= 15 and both minimal symptoms (ESS <10 and no self-reported falling asleep accident/near miss accident in the last 6 months) and lack of resistant hypertension

OR

AHI >=15 and either high symptom load (ESS>10 or self-reported falling asleep accident/near miss accident in the last 6 months) or resistant hypertension (elevated blood pressure despite >3 agents) requiring CPAP

Imaging of the coronary arteries will be performed following administration of an intravenous bolus of contrast on a computed tomography (CT) scanner capable of computed tomography coronary angiogram (CTCA) imaging doe by a trained radiographer at the Clinical Research Imaging Centre (CRIC) at baseline (day 1) (within 4 weeks of PSG) and 12 months in patients with coronary artery disease risk factors and symptoms suggestive of sleep apnoea. The CT scan will take about 30 minutes.
Intervention code [1] 301657 0
Not applicable
Comparator / control treatment
No or mild OSA (AHI index <15) not requiring CPAP (continuous positive airways pressure)
Control group
Active

Outcomes
Primary outcome [1] 306474 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in noncalcified plaque volume as determined by CTCA
Timepoint [1] 306474 0
12 months
Secondary outcome [1] 348636 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in total atheroma volume as determined by CTCA
Timepoint [1] 348636 0
12 months
Secondary outcome [2] 350253 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in calcified plaque volume as determined by CTCA
Timepoint [2] 350253 0
12 months
Secondary outcome [3] 350254 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in percent atheroma volume as determined by CTCA
Timepoint [3] 350254 0
12 months
Secondary outcome [4] 350255 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in maximum lumen stenosis as determined by CTCA
Timepoint [4] 350255 0
12 months
Secondary outcome [5] 350256 0
Compare the effects sleep apnoea treatment on the progression of coronary atherosclerosis
by measuring change in Leaman score as determined by CTCA
Timepoint [5] 350256 0
12 months

Eligibility
Key inclusion criteria
a. Able to provide written, informed consent
b. Age greater than or equal to 40 years of age
c. Evidence of established atherosclerotic cardiovascular disease
As evident by
i. History of myocardial infarction
ii. acute coronary syndrome
iii. arterial revascularization
OR
Risk Factor (One Required)
i. Cigarette smoking current?
ii. Hypertension (BP greater than or equal to 140/90 mm Hg or current use of antihypertensive medication)?
iii. Diabetes mellitus
iv. Low HDL cholesterol (men less than 1.0 mmol/l; women less than 1.3 mmol/l)
v. Family history of premature CHD (in first-degree male relative less than 55 years of age; in first-degree female relative less than 65 years of age
vi. Age (men: 50 years or older; women: 55 years or older)?
vii. hs-CRP greater than or equal to 2 mg/L
d. OSA diagnosed by polysomnography (PSG)
e. Treated with a stable dose of statin therapy for 4 weeks or more (dose can be zero)
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Inability to provide written, informed consent
b. Unwilling to be followed for serial CT evaluation
c. Chronic kidney disease (use of dialysis or eGRF <30 mL/min given the need to administer intravenous contrast)
d. Severe respiratory disease (severe chronic obstructive pulmonary disease, resting daytime SaO2 <90%)
e. New York Heart Association heart failure class III-IV
f. Prior coronary artery bypass grafting
g. Prior use of CPAP for OSA in the last 12 months
h. Central sleep apnea >5 events/hour
i. Significant comorbidity with a high likelihood of death in the next 12 months
j. Any condition that in the opinion of the responsible physician or investigator renders the participant unsuitable for the study E.g. severe disability; significant memory, perceptual, or behavioural disorder

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Baseline characteristics will be summarised descriptively with comparisons between OSA categories and plaque burden using a t-test (or Mann-Whitney’s U test if not normally distributed). Changes in volumetric plaque measures, lumen stenosis will be compared between the three treatment groups using analysis of covariance (ANCOVA) with baseline levels as a covariate. The primary endpoint parameter will be the change in noncalcified plaque volume. Secondary endpoints include changes in (i) total atheroma volume, (ii), calcified plaque volume, (iii) percent atheroma volume, (iv) maximum lumen stenosis, (v) Leaman score. Exploratory endpoints include changes in (i) metabolic risk factors, (ii) biomarkers reflecting inflammatory, endothelial and autonomic function and (iii) measures of CPAP therapy and OSA severity. Multivariable logistic regression models will examine (i) OSA severity as an independent predictor for plaque burden and (ii) degree of OSA therapy and changes in OSA severity as independent predictors of changes in plaque progression, adjusting for standard risk factors (age, gender, LDL-C, HDL-C, diabetes, smoking, BP), inflammatory [CRP]markers. Multivariable logistic regression models for plaque burden and progression will be developed using (i) traditional risk factors, (ii) risk factors and biomarkers (inflammatory, endothelial, autonomic), (iii) risk factors, biomarkers and plaque measures, (iv) risk factors, biomarkers, plaque measures, OSA severity and degree of CPAP adherence and (v) all potential predictors.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
There will be no other staff to continue the study once the student completes PhD.
Date of first participant enrolment
Anticipated
3/09/2018
Actual
Date of last participant enrolment
Anticipated
31/08/2019
Actual
Date of last data collection
Anticipated
5/09/2020
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11245 0
South Australian Health and Medical Research Institute (SAHMRI) - Adelaide
Recruitment postcode(s) [1] 23121 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299909 0
Other
Name [1] 299909 0
South Australian Health and Medical Research Institute (SAHMRI)
Country [1] 299909 0
Australia
Primary sponsor type
Other
Name
South Australian Health and Medical Research Institute (SAHMRI)
Address
North Terrace
Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 299290 0
None
Name [1] 299290 0
Address [1] 299290 0
Country [1] 299290 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 300778 0
Bellberry Limited
Ethics committee address [1] 300778 0
129 Glen Osmond Road
Eastwood, SA 5063
Ethics committee country [1] 300778 0
Australia
Date submitted for ethics approval [1] 300778 0
06/08/2018
Approval date [1] 300778 0
Ethics approval number [1] 300778 0

Summary
Brief summary
Several factors link OSA and atherosclerosis, including metabolic abnormalities, activation of inflammatory and oxidative pathways, autonomic dysfunction and mechanical factors linked to snoring. However, the relationship between OSA and its treatment with the burden and progression of atherosclerotic plaque has not been systematically investigated. Advances in computed tomography (CT) imaging permit noninvasive high-resolution plaque imaging, enabling characterisation of the factors driving disease progression. This study is an observational study of 75 adults to determine the relationship between OSA and its treatment with plaque burden, composition and progression. Imaging of the coronary arteries will be performed on a CT scanner at a baseline and 12 month follow-up visit. The baseline phase permits evaluation of the relationship between OSA and its severity with the extent, distribution and composition of plaque. The serial phase permits a real-world assessment of the impact of changes in OSA severity on plaque progression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84790 0
Ms Jordan Andrews
Address 84790 0
South Australian Health and Medical Research Institute
North Terrace
Adelaide, SA 5000
Country 84790 0
Australia
Phone 84790 0
+61 881284503
Fax 84790 0
Email 84790 0
[email protected]
Contact person for public queries
Name 84791 0
Ms Jordan Andrews
Address 84791 0
South Australian Health and Medical Research Institute
North Terrace
Adelaide, SA 5000
Country 84791 0
Australia
Phone 84791 0
+61 881284503
Fax 84791 0
Email 84791 0
[email protected]
Contact person for scientific queries
Name 84792 0
Ms Jordan Andrews
Address 84792 0
South Australian Health and Medical Research Institute
North Terrace
Adelaide, SA 5000
Country 84792 0
Australia
Phone 84792 0
+61 881284503
Fax 84792 0
Email 84792 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
study is not moving forward with recruitment


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.