Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001344381p
Ethics application status
Help: Ethics application status
Not yet submitted
Date submitted
Help: Date submitted
19/10/2026
Date registered
Help: Date registered
9/11/2026
Date last updated
Help: Date last updated
9/11/2026
Date data sharing statement initially provided
Help: Data sharing statement date
9/11/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
CLEAR-PFAS Study: A randomised controlled trial of regular plasma donation to reduce PFAS concentrations and non-calcified coronary plaque volume in adults with elevated PFAS exposure and non-calcified coronary artery plaque
Scientific title
CLEAR-PFAS study: A randomised controlled trial of immediate versus deferred regular plasma donation to reduce non-calcified coronary plaque volume in adults with elevated PFAS concentrations and non-calcified coronary plaque.
Additional trial identifiers [1] 318656 0
Nil
Universal Trial Number (UTN)
Trial acronym
CLEAR-PFAS
Related trial records

Health condition
Health condition(s) studied:
Coronary artery disease 343866 0
Atherosclerosis 343867 0
Per- and polyfluoroalkyl substance (PFAS) exposure 343868 0
Condition category
Condition code
Cardiovascular 340010 340010 0 0
Coronary heart disease
Public Health 340011 340011 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Intervention: Regular plasma donation (plasmapheresis)

Participants eligible for the intervention arm of the study will be randomised to immediate or deferred plasma donation. Participants randomised to immediate plasma donation will regularly donate plasma (plasmapheresis) for a 12-month period. In accordance with Australian national blood banking guidelines, the maximum allowable frequency of donations is once every 2 weeks (up to a maximum of 26 donations per rolling 12-month period). The exact timing and frequency of donations remain entirely at the participant's choice, provided this safety ceiling is not exceeded.

Participants must consult with their chosen donation facility to understand specific local requirements and eligibility criteria for plasmapheresis. Plasma donation will be performed face-to-face at a participant-nominated donation facility e.g. Australian Red Cross Lifeblood donor centre, in accordance with standard donor eligibility and safety requirements, requiring approximately 1.5 hours for the plasmapheresis procedure.

Plasma donation will be delivered by appropriately trained and credentialled donor centre staff operating under the policies and procedures of the donation facility. During each donation, whole blood will be collected, plasma separated using a plasmapheresis device, and the remaining blood components returned to the participant.

Intervention adherence will be assessed by study staff through participant-completed plasma donation logs and quarterly study contacts. Participants in both study groups will complete quarterly questionnaires throughout the 12-month study period.

Participants randomised to the immediate plasma donation group will record plasma donation dates in a plasma donation log, which will be reviewed by study staff during quarterly follow-up contacts.
Intervention code [1] 335555 0
Treatment: Other
Description of the comparator or control
Comparator: Deferred plasma donation
Participants allocated to the deferred intervention group will not undertake study-directed plasma donation during the initial 12-month study period and may commence plasma donation following completion of the 12-month follow-up assessments if they choose to do so.

Data collection will occur remotely via participant-completed questionnaires at quarterly intervals throughout the 12-month study period using their preferred mode of communication (emails or phone calls). Participants will also be asked to report any blood or plasma donations undertaken since the previous contact to assess adherence to the assigned treatment allocation.
Control group
Active

Outcomes
Primary outcome [1] 347170 0
Change in non-calcified plaque volume (mm3)
Timepoint [1] 347170 0
Baseline, 12-months after randomisation
Secondary outcome [1] 469249 0
Change in serum total PFAS concentration
Timepoint [1] 469249 0
Baseline, 12-months after randomisation
Secondary outcome [2] 469250 0
Change in total atheroma volume
Timepoint [2] 469250 0
Baseline, 12-months after randomisation
Secondary outcome [3] 469251 0
Change in calcified plaque volume
Timepoint [3] 469251 0
Baseline, 12-months after randomisation
Secondary outcome [4] 469252 0
Change in percent atheroma volume
Timepoint [4] 469252 0
Baseline, 12-months after randomisation
Secondary outcome [5] 469255 0
Change in health-related quality of life
Timepoint [5] 469255 0
Baseline, 12 months after randomisation
Secondary outcome [6] 469256 0
Incident cardiovascular events during the 12-month study period (myocardial infarction, coronary revascularisation, hospitalisation for unstable angina, stroke/transient ischaemic attack, or cardiovascular-related mortality)
Timepoint [6] 469256 0
12-months after randomisation
Secondary outcome [7] 469447 0
Change in peri-coronary fat attenuation index.
Timepoint [7] 469447 0
Baseline, 12-months after randomisation

Eligibility
Key inclusion criteria
- Aged 45 - 73 years
- Able and willing to provide written informed consent
- Serum concentration of one or more specified PFAS analytes (PFOA, PFOS, or PFHxS) greater than or equal to the 75th percentile of the relevant National Health and Measures Survey (NHMS) reference values, confirmed by a study-specific baseline PFAS test.
- PFAS blood test performed during screening/baseline assessment.
- Presence of non-calcified coronary plaque on study coronary CT angiography (CCTA) performed during screening/baseline assessment.
- Willing to be randomised to either immediate or deferred initiation of plasma donation.
- Willing to undertake regular plasma donation if deemed eligible by the donation facility.
Minimum age
45 Years
Maximum age
73 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
- Previous acute coronary syndrome, myocardial infarction, or coronary revascularisation (PCI or CABG).
- Currently undertaking, or unwilling to abstain during the study period from, PFAS-lowering activities other than the study intervention, including but not limited to regular blood or plasma donation, therapeutic apheresis, bile acid sequestrant therapy (e.g. cholestyramine)
- Medical contraindication to regular plasma donation (e.g., severe anaemia, haemodynamic instability, known coagulopathy)
- Blood or plasma donation within 3 months prior to randomisation
- Medical condition requiring therapeutic apheresis
- Any medical condition which, in the investigator’s judgement, would prevent completion of the 12-month study period
- Known contraindication to coronary CT angiography (CCTA), including eGFR <30 mL/min/1.73m2, contrast allergy, inability to perform an adequate breath-hold or body habitus precluding diagnostic image acquisition

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random allocation sequence using stratified permuted block randomisation. Randomisation will be stratified by age and sex. Within each stratum, allocation will use random permuted blocks of varying size. Block sizes will be determined by the study statistician and will not be disclosed to study staff or investigators to maintain allocation concealment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: The study is powered to detect a clinically meaningful between-group difference of 7.6 mm³ in change in non-calcified coronary plaque volume between the immediate plasma donation and deferred plasma donation groups. The effect size is based on a meta-analysis of serial coronary CT angiography studies reporting statin-associated reductions in non-calcified plaque volume.
Assuming a standard deviation of 15.6 mm³, analysis of covariance (ANCOVA) adjustment for baseline plaque volume, a two-sided alpha of 0.05, 80% power, and 1:1 allocation, 45 participants per group are required. Allowing for 20% attrition, 57 participants per group (114 participants in total) will be randomised.

Statistical analysis: Analyses will follow the intention-to-treat principle. The primary analysis will compare groups on 12-month non-calcified plaque volume using ANCOVA, with baseline non-calcified plaque volume included as a covariate and randomisation arm as the factor of interest. Secondary imaging and biochemical outcomes will be analysed using similar ANCOVA models, adjusted for their corresponding baseline values. Missing data will be handled according to a prespecified Statistical Analysis Plan.
A pre-specified secondary analysis will examine the dose-response relationship between achieved reduction in serum PFAS concentrations and change in non-calcified plaque volume.
Detailed analytical methods will be specified in the Statistical Analysis Plan.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2027
Actual
Date of last participant enrolment
Anticipated
31/12/2027
Actual
Date of last data collection
Anticipated
28/02/2029
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 323232 0
Government body
Name [1] 323232 0
National Health and Medical Research Council (NHMRC)
Country [1] 323232 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 326200 0
None
Name [1] 326200 0
Address [1] 326200 0
Country [1] 326200 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 321629 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 321629 0
Ethics committee country [1] 321629 0
Australia
Date submitted for ethics approval [1] 321629 0
16/11/2026
Approval date [1] 321629 0
Ethics approval number [1] 321629 0
2026/ETH02292

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

Contacts
Principal investigator
Name 154322 0
Prof Gemma Figtree
Address 154322 0
Sydney Medical School (Northern) Cardiology Department, Royal North Shore Hospital Reserve Road, St Leonards NSW 2065 Australia
Country 154322 0
Australia
Phone 154322 0
+61 2 9926 4915
Fax 154322 0
Email 154322 0
[email protected]
Contact person for public queries
Name 154323 0
Gemma Figtree
Address 154323 0
Sydney Medical School (Northern) Cardiology Department, Royal North Shore Hospital Reserve Road, St Leonards NSW 2065 Australia
Country 154323 0
Australia
Phone 154323 0
+61 2 9926 4937
Fax 154323 0
Email 154323 0
[email protected]
Contact person for scientific queries
Name 154324 0
Gemma Figtree
Address 154324 0
Sydney Medical School (Northern) Cardiology Department, Royal North Shore Hospital Reserve Road, St Leonards NSW 2065 Australia
Country 154324 0
Australia
Phone 154324 0
+61 2 9926 4915
Fax 154324 0
Email 154324 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.