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Trial registered on ANZCTR


Registration number
ACTRN12620000100998
Ethics application status
Approved
Date submitted
9/01/2020
Date registered
5/02/2020
Date last updated
5/02/2020
Date data sharing statement initially provided
5/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Testosterone for Atherosclerosis Reduction (T4AR)
Scientific title
Testosterone for Atherosclerosis Reduction (T4AR): a multicentre, randomised, double blind, placebo-controlled 2-year trial to determine if testosterone (Reandron®) therapy reduces progression of coronary atheroma in middle-aged and older men.
Secondary ID [1] 300219 0
Nil known
Universal Trial Number (UTN)
Trial acronym
T4AR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary atheroma 315778 0
Coronary atherosclerosis 315779 0
Condition category
Condition code
Cardiovascular 314063 314063 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Testosterone undecanoate (Reandron®, Bayer Australia Ltd) 1000 mg/4 ml solution deep intramuscular injection administered at baseline, six weeks after, then every 12 weeks. Total duration of trial is 2 years. Dose administered is 4 mls of 250 mg/ml, 1000 mg testosterone undecanoate in total, site of administration buttock.
Intervention code [1] 316492 0
Treatment: Drugs
Comparator / control treatment
Placebo 4ml solution deep intramuscular injection administered at baseline, six weeks after, then every 12 weeks. Total duration of the trial is 2 years. Composition is benzyl benzoate and castor oil, total 4 ml volume administered, site of administration buttock.
Control group
Placebo

Outcomes
Primary outcome [1] 322460 0
Changes in volume of non-calcified coronary atheromatous plaque from baseline to end of intervention period as measured by Cardiac Computed Tomography Angiography (CCTA)

Timepoint [1] 322460 0
Two years from first study injection
Secondary outcome [1] 378606 0
Low attenuation plaque (<30 Hounsfield Units) assessed using CCTA
Timepoint [1] 378606 0
Two years from first study injection
Secondary outcome [2] 378607 0
Spotty calcification (<3mm in size) assessed using CCTA
Timepoint [2] 378607 0
Two years from first study injection
Secondary outcome [3] 378608 0
Napkin ring sign assessed using CCTA
Timepoint [3] 378608 0
Two years from first study injection
Secondary outcome [4] 378609 0
Plaque Remodelling Index (PRI) >1.10 assessed using CCTA
Timepoint [4] 378609 0
Two years from first study injection

Eligibility
Key inclusion criteria
Men aged 50-74 years
Waist circumference greater than or equal to 95 cm
No known reproductive pathology or CVD
Baseline testosterone less than or equal to 14 nmol/L
Able and willing to meet protocol requirements, read and understand the Participant Information and Consent Form and provide informed consent
Minimum age
50 Years
Maximum age
74 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Age greater than or equal to 75 years (to exclude older men more likely to be frail or have limited mobility)
Presence of hypothalamic, pituitary or testicular disease
Use of androgens or anti-androgen therapy within past 12 months
Known CVD (established angina, MI, heart failure, stroke, transient ischaemic attack or coronary or carotid artery revascularisation)
Previous unprovoked deep vein thrombosis or pulmonary embolism
Current anticoagulation (relative contraindication for deep intramuscular injections: use of aspirin in low-moderate dose, or fish oil, are not exclusions)
Any malignancy apart from non-melanoma skin cancer
Untreated hyper- or hypothyroidism
Diabetes mellitus requiring the use of insulin
Ongoing episode of major depression or other significant psychiatric disorder
Excessive alcohol intake (greater than or equal to 14 standard drinks/week)
Use of medications known to affect the production or action of testosterone (e.g. GnRH agonists, spironolactone, or regular opioids) or sex hormone binding globulin (e.g. insulin, growth hormone, antiepileptics, thyroid hormone)
Major systemic illnesses (e.g. HIV infection, chronic viral hepatitis)
Previous (within past 5 years) or planned bariatric surgery

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 304650 0
University
Name [1] 304650 0
The University of Western Australia
Address [1] 304650 0
35 Stirling Highway
CRAWLEY WA 6009
Country [1] 304650 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Highway
CRAWLEY WA 6009
Country
Australia
Secondary sponsor category [1] 304952 0
None
Name [1] 304952 0
Address [1] 304952 0
Country [1] 304952 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305070 0
South Metropolitan Health Service (Fiona Stanley Hospital)
Ethics committee address [1] 305070 0
11 Robin Warren Drive
MURDOCH WA 6150
Ethics committee country [1] 305070 0
Australia
Date submitted for ethics approval [1] 305070 0
Approval date [1] 305070 0
02/12/2019
Ethics approval number [1] 305070 0

Summary
Brief summary
To determine whether Testosterone (T) treatment versus placebo will reduce progression of subclinical coronary atherosclerosis in middle aged and older men without reproductive pathology or known CardioVascular Disease (CVD). The main aim is to discover whether T therapy over two years results in smaller increases in the volume of non-calcified coronary atheromatous plaque, as measured by Cardiac Computed Tomography Angiography (CCTA) versus placebo. A secondary aim is to determine whether T therapy improves high risk plaque (HRP) characteristics, also assessed using CCTA versus placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99166 0
Prof Bu Yeap
Address 99166 0
The University of Western Australia (M704)
35 Stirling Highway
CRAWLEY WA 6009
Country 99166 0
Australia
Phone 99166 0
+61 8 6151 1148
Fax 99166 0
Email 99166 0
bu.yeap@uwa.edu.au
Contact person for public queries
Name 99167 0
Ms Shuen-Chyn Soh
Address 99167 0
The University of Western Australia (M570)
35 Stirling Highway
CRAWLEY WA 6009
Country 99167 0
Australia
Phone 99167 0
+61 8 6151 1138
Fax 99167 0
Email 99167 0
shuen-chyn.soh@uwa.edu.au
Contact person for scientific queries
Name 99168 0
Prof Bu Yeap
Address 99168 0
The University of Western Australia (M704)
35 Stirling Highway
CRAWLEY WA 6009
Country 99168 0
Australia
Phone 99168 0
+61 8 6151 1148
Fax 99168 0
Email 99168 0
bu.yeap@uwa.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
No IPD sharing is planned
What supporting documents are/will be available?
No other documents available
Summary results
No Results