ANZCTR - Registration

Please note that the copy function is not enabled for this field.
If you wish to modify existing outcomes, please copy and paste the current outcome text into the Update field.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12619000204145

Ethics application status

Approved

Date submitted

6/02/2019

Date registered

12/02/2019

Date last updated

17/06/2022

Date data sharing statement initially provided

12/02/2019

Date results information initially provided

17/09/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

A study examining the effect of blood and plasma donation on serum per- and poly-fluoroalkyl substances (PFAS) levels in Metropolitan Fire Brigade staff

Scientific title

A randomised controlled trial examining the effect of blood and plasma donation on serum per- and poly-fluoroalkyl substances (PFAS) levels in Metropolitan Fire Brigade staff

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

per- and poly-fluoroalkyl substances (PFAS) contamination

Condition category

Condition code

Public Health

Other public health

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be randomised to one of three groups.
Group one will donate blood every 12 weeks for 12 months, group two will donate plasma every 6 weeks for 12 months and group three will undergo no intervention.
Participants will have their donations checked by the study coordinator.

Intervention code [1]

Treatment: Other

Comparator / control treatment

Participants in the control group will not donate blood or plasma, and will have their PFAS levels reassessed at the end of the study period.

Control group

Active

Outcomes

Primary outcome [1]

To identify whether there is a significant change in serum PFOS levels after 12 months of whole blood or plasma donation compared to observation, within and between groups.

Timepoint [1]

After 12 months of intervention

Primary outcome [2]

To identify whether there is a significant change in serum PFHxS levels after 12 months of whole blood or plasma donation compared to observation, within and between groups.

Timepoint [2]

After 12 months of donations

Secondary outcome [1]

Changes in serum PFAS (PFOS or PFHxS) levels in each group from post-test to 3-month follow-up.

Timepoint [1]

Difference between serum PFAS level after 12 months of intervention and the level a further 3 months later.

Secondary outcome [2]

Differences in serum total cholesterol between whole blood donation, plasma donation and control groups.

Timepoint [2]

After 12 months of the intervention.

Secondary outcome [3]

Differences in serum thyroid stimulating hormone (TSH) levels between whole blood donation, plasma donation and control groups.

Timepoint [3]

After 12 months of the intervention.

Secondary outcome [4]

Differences in serum bilirubin between whole blood donation, plasma donation and control groups.

Timepoint [4]

After 12 months of the intervention.

Secondary outcome [5]

Differences in serum creatinine between whole blood donation, plasma donation and control groups.

Timepoint [5]

After 12 months of the intervention.

Secondary outcome [6]

Differences in serum LDL between whole blood donation, plasma donation and control groups.

Timepoint [6]

After 12 months of the intervention.

Secondary outcome [7]

Differences in serum HDL between whole blood donation, plasma donation and control groups.

Timepoint [7]

After 12 months of the intervention.

Secondary outcome [8]

Differences in serum triglycerides between whole blood donation, plasma donation and control groups.

Timepoint [8]

After 12 months of the intervention.

Secondary outcome [9]

Differences in serum thyroxine (T4) between whole blood donation, plasma donation and control groups.

Timepoint [9]

After 12 months of the intervention.

Secondary outcome [10]

Differences in serum triiodothyronine (T3) between whole blood donation, plasma donation and control groups.

Timepoint [10]

After 12 months of the intervention.

Secondary outcome [11]

Differences in serum alanine aminotransferase (ALT) between whole blood donation, plasma donation and control groups.

Timepoint [11]

After 12 months of the intervention.

Secondary outcome [12]

Differences in serum aspartate aminostransferase (AST) between whole blood donation, plasma donation and control groups.

Timepoint [12]

After 12 months of the intervention.

Secondary outcome [13]

Differences in serum gamma-glutamyl transferase (GGT) between whole blood donation, plasma donation and control groups.

Timepoint [13]

After 12 months of the intervention.

Secondary outcome [14]

Differences in serum albumin between whole blood donation, plasma donation and control groups.

Timepoint [14]

After 12 months of the intervention.

Secondary outcome [15]

Change in serum levels of other PFAS chemicals, this is an exploratory outcome and will include (but is not be limited to) PFOA, PFBS, PFPeS, PFHpS, PFDS, PFBA, PFPeA, PFHxA, PFHpA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 10:2 FTS, FOSA 10, MeFOSA, EtFOSA, MeFOSE, EtFOSE, MeFOSAA, EtFOSAA

Timepoint [15]

After 12 months and 15 months

Secondary outcome [16]

Difference in serum PFOS levels between whole blood and plasma donation.

Timepoint [16]

12 months

Secondary outcome [17]

Difference in serum PFHxS levels between whole blood and plasma donation.

Timepoint [17]

After 12 months of donation

Eligibility

Key inclusion criteria

1. Metropolitan Fire Brigade staff with 10 or more years of previous occupational exposure to PFAS.

2. PFOS levels >=5ng/mL

3. Eligible to donate blood (in accordance with the ARCBS guidelines).

4. Not donated blood in the past 3 months.

5. Signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial prior to enrolment.

6. Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures.

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Medical contraindication to blood donation.

2. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant inappropriate for entry into this study.

3. Previous ineligibility to donate blood.

4. Planned travel or extended leave (e.g. >6 weeks) that would prevent access to blood donation facilities.

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)

Randomisation will be conducted by the study statistician off-site, and participants will be informed of their group allocation by mail.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

We will use covariate-adaptive randomisation to balance participants' sex and blood PFAS levels between the three groups, randomising subjects as the results from the analyses of the baseline PFAS screening are received from the lab.

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

We would consider a 25% reduction in serum PFAS levels to be significant after 12 months of plasma or whole blood donation. Based on the serum levels of PFHxS, PFOS, and PFOA found in 149 Australian firefighters in Rotander et al. (2015), and a correlation between the assessments at baseline and 12 months (post-test) of r = .6, this corresponds to a standardised effect size of mean difference dz > .31. We would require each group to have 94 participants to have 90% power to detect a 25% reduction in PFAS levels.

In order to test whether plasma donation reduces serum PFAS levels at a faster rate than whole blood donation, we would require each group to have 105 participants at pre-test for 90% power to detect a conventional small effect size (partial eta-squared of .01) difference between the groups from pre-test to post-test.

To further compare the efficacy of plasma donation and whole blood donation to the observation only group (control), a sample of 105 participants per group would provide 80% power to detect the same small effect size (and 90% power to detect partial n squared = .013) after correction for multiple testing.

We have planned our analyses based on intention-to-treat and will use multiple imputation to handle missing data. Our power analyses are conservative to account for the possibility of inflated Type II error and indicate a required total sample size of 315 participants (105 per group). The protocol is designed to allow for up to 10% of participants being lost to follow-up over the life of the project.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/03/2019

Actual

24/05/2019

Date of last participant enrolment

Anticipated

31/08/2019

Actual

23/08/2019

Date of last data collection

Anticipated

31/03/2021

Actual

26/03/2021

Sample size

Target

315

Accrual to date

Final

285

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Metropolitan Fire Brigade

Address [1]

456 Albert Street
East Melbourne Vic 3002

Country [1]

Australia

Primary sponsor type

University

Name

Macquarie University

Address

Balaclava Rd, Macquarie Park NSW 2109

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Macquarie University; Macquarie University Human Research Ethics Committee (Medical Sciences).

Ethics committee address [1]

17 Wally's Walk
Macquarie University
NSW 2109

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/11/2018

Approval date [1]

17/12/2018

Ethics approval number [1]

3855

Summary

Brief summary

This is a study to assess the effect of 12 months of blood or plasma donation on serum PFAS levels in a cohort of Metropolitan Fire Brigade (MFB) firefighters.

The purpose of the study is to determine if regular blood donation (i.e. whole blood, or plasma donation) will be effective in reducing serum PFAS levels.

Participants will be randomly allocated into one of the following three groups: a whole blood donation, a plasma donation or an observation only for a 12-month period.

Group 1: Blood donation every 12 weeks

Group 2: Plasma donation every 6 weeks

Group 3: Observation alone

The study will run for a total of 18 months (approximately 3 months screening and randomisation, 12 months intervention and 3 months follow up).

Trial website

https://www.mq.edu.au/about/about-the-university/faculties-and-departments/medicine-and-health-sciences/departments-and-centres/department-of-clinical-medicine/pfas-clinical-study

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Robin Gasiorowski

Address

Senior Lecturer, Haematology
Department of Clinical Medicine
2 Technology Place
Macquarie University
NSW 2109

Country

Australia

Phone

+61 (2) 9812 2981

Fax

Email

[email protected]

Contact person for public queries

Name

Dr Robin Gasiorowski

Address

Senior Lecturer, Haematology
Department of Clinical Medicine
2 Technology Place
Macquarie University
NSW 2109

Country

Australia

Phone

+61 (2) 9812 2981

Fax

Email

[email protected]

Contact person for scientific queries

Name

Dr Robin Gasiorowski

Address

Senior Lecturer, Haematology
Department of Clinical Medicine
2 Technology Place
Macquarie University
NSW 2109

Country

Australia

Phone

+61 (2) 9812 2981

Fax

Email

[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

As this study is recruiting from a relatively small, defined population there is concern that individuals may be able to be identified from their IPD, even though it will be de-identified.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
16405	Study protocol	Silver G, Krastev Y, Forbes MK, et alStudy protocol for a randomised controlled trial examining the effect of blood and plasma donation on serum perfluoroalkyl and polyfluoroalkyl substance (PFAS) levels in firefightersBMJ Open 2021;11:e044833. doi: 10.1136/bmjopen-2020-044833	https://bmjopen.bmj.com/content/11/5/e044833

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Gasiorowski R, Forbes MK, Silver G, et al. Effect ... [More Details]	376871-(Uploaded-15-06-2022-15-49-12)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Study protocol for a randomised controlled trial examining the effect of blood and plasma donation on serum perfluoroalkyl and polyfluoroalkyl substance (PFAS) levels in firefighters.	2021	https://dx.doi.org/10.1136/bmjopen-2020-044833
Dimensions AI	Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia	2022	https://doi.org/10.1001/jamanetworkopen.2022.6257

N.B. These documents automatically identified may not have been verified by the study sponsor.