ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12625000663459p

Ethics application status

Not yet submitted

Date submitted

28/05/2025

Date registered

23/06/2025

Date last updated

23/06/2025

Date data sharing statement initially provided

23/06/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

PRE-TREAT: A clinical trial exploring if a combination inhaler prevents early lung changes from developing into full chronic obstructive pulmonary disease (COPD).

Scientific title

Does inhaled triple therapy in individuals with pre-COPD arrest progression to full-blown COPD? A double-blind randomised placebo-controlled trial (PRE-TREAT)

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

PRE-TREAT

Linked study record

Health condition

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

Pre-COPD

Condition category

Condition code

Respiratory

Chronic obstructive pulmonary disease

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

A triple therapy inhaler that includes three medicines, i.e., inhaled corticosteroid (ICS, e.g., fluticasone furoate), + long-acting muscarinic antagonist (LAMA, e.g., umeclidinium), and long-acting beta-agonist (LABA, e.g., vilanterol). Each inhalation will include fluticasone furoate 100 mcg, umeclidinium 62.5 mcg and vilanterol 25 mcg. Dose is one puff once a day for 12 months. Adherence will be monitored through regular check-ups via phone calls/emails/dairies, as well as return of empty inhalers.

Intervention code [1]

Prevention

Comparator / control treatment

Placebo (sham inhalers, aerosol propellant only).

Control group

Placebo

Outcomes

Primary outcome [1]

Change in post-bronchodilator forced expiratory volume in 1 second (post-BD FEV1) from baseline to 12 months, post-randomisation.

Timepoint [1]

Baseline and 12 months post-randomisation.

Secondary outcome [1]

Change in post-BD forced vital capacity (FVC) from baseline to 12 months post-randomisation.

Timepoint [1]

Baseline and 12 months post-randomisation.

Secondary outcome [2]

Change in post-BD FEV1/FVC from baseline to 12 months post-randomisation.

Timepoint [2]

Baseline and 12 months post-randomisation.

Secondary outcome [3]

Change in Maximum Expiratory Flow at 25-75% of vital capacity (MEF25-75) from baseline to 12 months post-randomisation.

Timepoint [3]

Baseline and 12 months post-randomisation.

Secondary outcome [4]

Change in concavity index from baseline to 12 months post-randomisation.

Timepoint [4]

Baseline and 12 months post-randomisation.

Secondary outcome [5]

Change in resistance from baseline to 12 months post-randomisation.

Timepoint [5]

Baseline and 12 months post-randomisation.

Secondary outcome [6]

Change in respiratory symptoms from baseline to 12 months post-randomisation, this will be assessed as a composite outcome.

Timepoint [6]

Baseline and 12 months post-randomisation.

Secondary outcome [7]

Change in quality of life from baseline to 12 months post-randomisation

Timepoint [7]

Baseline and 12 months post-randomisation

Secondary outcome [8]

Change in reactance from baseline to 12 months post-randomisation

Timepoint [8]

Baseline and 12 months post-randomisation

Eligibility

Key inclusion criteria

Tasmania Longitudinal Health Study (TAHS) participants who belong to a pre-COPD lung function trajectory (a higher rate of lung function decline plus a high risk of COPD), were defined using longitudinal modelling of FEV1 or FEV1/FVC.

Minimum age

60 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

Systemic steroid use <28 days before enrolment, current use of any of the generic triple therapy (TT) components, COPD (FEV1/FVC ratio less than the lower limit of normal)

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Inhaler distribution will be centralised. SyntroHealth will label the inhalers according to the randomisation list provided by the independent statistician (via either using a CSV file or sealed opaque envelopes).

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

Randomisation of eligible consented participants will be performed using randomly permuted blocks of varying sizes in a 1:1 ratio, stratified by centre and smoking status. The randomisation list will be computer-generated by an independent statistician and carried out centrally using an electronic database to ensure concealment.

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
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 2 / Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

A formal statistical analysis plan will be written by the trial biostatistician and published on our research centre’s website while blind to group allocation. Analyses will be conducted on an intention-to-treat basis, comparing the groups as randomised, and per-protocol analyses will be conducted as sensitivity analyses.
The primary outcome will be analysed using a constrained longitudinal data analysis (cLDA) model. The response will consist of all post-BD FEV1 measures (at baseline, 6, and 12 months), and the model will include factors representing treatment group, time (categorical), and group-by-time interaction, with the restriction of a common baseline mean across treatment groups. The mean change in post-BD FEV1 from baseline to each follow-up time point, between the intervention group compared to the control group, will be obtained.
The primary hypothesis will be evaluated by obtaining the estimated difference between intervention and control groups in mean change in post-BD FEV1 from baseline to 12 months post-randomisation, a two-sided 95% confidence interval, and a p-value. Heterogeneity of the treatment effect will be explored for subgroups (baseline characteristics as defined in secondary aim), by including an interaction term between treatment and subgroup in the model.
All secondary and biomarker outcomes will be analysed similarly to the primary outcome. These models provide valid inference in the presence of missing data, if data are missing at random. Analysis will be conducted using the delta-adjustment method under the pattern-mixture modelling framework in the context of multiple imputation to assess sensitivity to missingness not at random. Models will be adjusted for stratification factors, centre, and smoking status. Adverse health events will be summarised using frequency and percentages.
Secondary data analyses of treatment response and disease progression defined by changes in symptoms, lung function and CT over the study period, will be conducted by our biostatistician. Baseline profiles as potential modifiers (novel traits) of these two outcomes will be identified by finite mixture model analysis. Predictive risk-models and risk score charts for treatment response and disease progression will be developed using random forest modelling and Classification and Regression Tree (CART) analysis.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/01/2026

Actual

Date of last participant enrolment

Anticipated

31/12/2026

Actual

Date of last data collection

Anticipated

31/12/2027

Actual

Sample size

Target

500

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

TAS

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

The University of Melbourne

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

Country [1]

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

Monash Health Human Research Ethics Committee A

Ethics committee address [1]

https://monashhealth.org/research/resources/resource-library/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/10/2025

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Chronic Obstructive Pulmonary Disease (COPD) is a severe condition causing millions of deaths annually, with late diagnosis and progressive lung damage making current treatments only symptomatic. The trial focuses on the pre-COPD phase, a critical period when lung function begins to decline but before permanent damage occurs, offering an opportunity for intervention. Inhaled Triple Therapy (fluticasone furoate, umeclidinium, and vilanterol) may slow lung function decline and prevent progression to COPD. This double-blind, randomized, placebo-controlled trial will involve 500 participants from the Tasmanian Longitudinal Health Study (TAHS) to evaluate the therapy's effectiveness and cost efficiency. If successful, this groundbreaking study could shift COPD management to prevention, reduce its global burden, and lay the foundation for future research and drug development.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Shyamali Dharmage

Address

Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010

Country

Australia

Phone

+61 383 440 737

Fax

Email

[email protected]

Contact person for public queries

Name

Shyamali Dharmage

Address

Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010

Country

Australia

Phone

+61 383 440 737

Fax

Email

[email protected]

Contact person for scientific queries

Name

Shyamali Dharmage

Address

Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010

Country

Australia

Phone

+61 383 440 737

Fax

Email

[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.