Trial Review

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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] 314434 0
None
Universal Trial Number (UTN)
Trial acronym
PRE-TREAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pre-COPD 337457 0
Condition category
Condition code
Respiratory 333831 333831 0 0
Other respiratory disorders / diseases
Respiratory 333830 333830 0 0
Chronic obstructive pulmonary disease

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] 331048 0
Prevention
Comparator / control treatment
Placebo (sham inhalers, aerosol propellant only).
Control group
Placebo

Outcomes
Primary outcome [1] 341438 0
Change in post-bronchodilator forced expiratory volume in 1 second (post-BD FEV1) from baseline to 12 months, post-randomisation.
Timepoint [1] 341438 0
Baseline and 12 months post-randomisation.
Secondary outcome [1] 448579 0
Change in resistance from baseline to 12 months post-randomisation.
Timepoint [1] 448579 0
Baseline and 12 months post-randomisation.
Secondary outcome [2] 447511 0
Change in concavity index from baseline to 12 months post-randomisation.
Timepoint [2] 447511 0
Baseline and 12 months post-randomisation.
Secondary outcome [3] 447506 0
Change in post-BD forced vital capacity (FVC) from baseline to 12 months post-randomisation.
Timepoint [3] 447506 0
Baseline and 12 months post-randomisation.
Secondary outcome [4] 448583 0
Change in quality of life from baseline to 12 months post-randomisation
Timepoint [4] 448583 0
Baseline and 12 months post-randomisation
Secondary outcome [5] 447508 0
Change in Maximum Expiratory Flow at 25-75% of vital capacity (MEF25-75) from baseline to 12 months post-randomisation.
Timepoint [5] 447508 0
Baseline and 12 months post-randomisation.
Secondary outcome [6] 447507 0
Change in post-BD FEV1/FVC from baseline to 12 months post-randomisation.
Timepoint [6] 447507 0
Baseline and 12 months post-randomisation.
Secondary outcome [7] 448764 0
Change in reactance from baseline to 12 months post-randomisation
Timepoint [7] 448764 0
Baseline and 12 months post-randomisation
Secondary outcome [8] 448582 0
Change in respiratory symptoms from baseline to 12 months post-randomisation, this will be assessed as a composite outcome.
Timepoint [8] 448582 0
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] 318962 0
Government body
Name [1] 318962 0
NHMRC
Country [1] 318962 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 321433 0
None
Name [1] 321433 0
None
Address [1] 321433 0
Country [1] 321433 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 317572 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 317572 0
Ethics committee country [1] 317572 0
Australia
Date submitted for ethics approval [1] 317572 0
01/10/2025
Approval date [1] 317572 0
Ethics approval number [1] 317572 0

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

Contacts
Principal investigator
Name 141466 0
Prof Shyamali Dharmage
Address 141466 0
Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010
Country 141466 0
Australia
Phone 141466 0
+61 383 440 737
Fax 141466 0
Email 141466 0
[email protected]
Contact person for public queries
Name 141467 0
Shyamali Dharmage
Address 141467 0
Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010
Country 141467 0
Australia
Phone 141467 0
+61 383 440 737
Fax 141467 0
Email 141467 0
[email protected]
Contact person for scientific queries
Name 141468 0
Shyamali Dharmage
Address 141468 0
Level 3, 207 Bouverie Street, The University of Melbourne, Victoria 3010
Country 141468 0
Australia
Phone 141468 0
+61 383 440 737
Fax 141468 0
Email 141468 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.