Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000766718
Ethics application status
Approved
Date submitted
10/05/2022
Date registered
30/05/2022
Date last updated
20/06/2024
Date data sharing statement initially provided
30/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeting Treatable Traits (TTs) in Chronic Obstructive Pulmonary Disease (COPD) to Prevent Hospitalisations.
Scientific title
A cluster randomised controlled trial evaluating the efficacy of a practice nurse-coordinated intervention targeting treatable traits in moderate-severe COPD in primary care, compared with usual care, and its effect on health-related quality of life (HRQoL) and hospitalisations/emergency department (ED) visits
Secondary ID [1] 306838 0
ISS 10845
Universal Trial Number (UTN)
Trial acronym
TERRACOTTA (Targeting Treatable Traits in COPD to Prevent Hospitalisations)
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 325928 0
chronic bronchitis 325929 0
emphysema 325930 0
Asthma-COPD Overlap 325931 0
Condition category
Condition code
Respiratory 323238 323238 0 0
Chronic obstructive pulmonary disease
Respiratory 323239 323239 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention (TERRACOTTA) participants will undergo a multidimensional assessment at baseline with the practice nurse to characterise TTs across pulmonary, extra-pulmonary, and behavioural/risk factor domains. A case management meeting will then be organised between the practice nurse and participant to plan the delivery of the intervention. The intervention will comprise:
1. mHealth: A specifically designed application installed on the personal mobile phone to record symptoms and medication usage on a weekly basis will be used by the participants for 12 months. Participants will also be prompted to follow an individualized written action plan specifically developed by the study team. The CSIRO AHERC has designed similar innovative mHealth solutions for optimising care delivery for individuals with chronic diseases, which will be utilised in this trial. Each participant will have their own profile compiled through the portal, to ensure that the app is tailored and individualised according to their specific needs. An automated feedback message will be sent weekly according to an algorithm based on guidelines. An automated weekly message of overall COPD control will be displayed as ‘well-controlled’ (green zone), or ‘not well controlled’ (yellow or orange zone) or ‘very poorly controlled’ (red zone), to encourage participants to follow their agreed written action plan. All data will be transmitted automatically to a central server of CSIRO to which participants and their health professionals have secure access.
2. Home-based pulmonary rehabilitation (HomeBase): This rehabilitation program involves 8 weeks of individually prescribed exercise training and self-management education delivered by a physiotherapist. The model includes one home visit (approximately 2 hours) by the physiotherapist, followed by weekly follow-up telephone calls using a motivational interviewing approach to build confidence and set goals. Home based exercise training is prescribed based on each patient’s exercise capacity, walking distance is assessed using pedometers and participants record their daily walking in a diary or mHealth app. Participants will be encouraged to exercise for 30 minutes, five times per week. Exercise intensity is symptom guided, with a target of moderate to somewhat severe dyspnoea rated on the Borg scale. Strength training utilizes activities that can easily be performed at home, such as stair training and sitting to standing from a chair. Participants will be telephoned weekly by the physiotherapist to (1) review the home diary/mHealth app; (2) progress the exercise prescription; and (3) for self-management education. Self-management training will include managing acute exacerbations; monitoring exercise; managing breathlessness; and accessing community supports. On completion of the program, participants will be encouraged to continue with external peer support and social group for people with COPD (e.g. LFA’s Lungs in Action program).
3. Home Medication Review (HMR): A comprehensive HMR from a consultant pharmacist will identify any medication-related problems and deviations from COPD-X. The pharmacist will visit patients at their home (a single 1.5 hour visit), assess medication adherence and inhaler techniques, educate visually and verbally (with the help of infographics available from Lung Foundation Australia/NPS Medicinewise and educational materials developed specifically for the study) on role of medications in management of COPD, management of comorbidities and behavioural risk factors (e.g. smoking, non-adherence) and recommend strategies for improving medication use (e.g. developing routines, using reminders). A written report will be sent to the practice nurse and GP. A case conference will be organised after one month among the pharmacist, the GP and the practice nurse, to review the recommendations and changes in management.
4. Written action plan: The practice nurse and GP will work with each participant (face-to-face for 30 minutes) to design a written action plan consistent with COPDX guidelines based on information obtained at baseline. It will contain instructions on which medications to take when feeling well, how to recognise worsening disease using peak-flow meters/portable electronic micro-spirometers and/or symptoms, what to do when symptoms are getting worse and in the event of an acute exacerbation, a first aid plan. Where appropriate, each participant’s GP will also give a script for oral steroids/antibiotics, which can be initiated after discussion with the practice nurse, who will assess the need based on symptoms and/or lung function.
5. Smoking cessation support: The practice nurse will coordinate individualised intensive smoking cessation support (duration ~15 minutes) comprising pharmacotherapy and behavioural support to all current smokers based on the RACGP guidelines. The intervention(s) offered will be individually tailored to the patient’s smoking status, needs and preferences. If prescription medications (e.g. varenicline) are required to assist quitting, these will be discussed with the participant’s GP. Smoking cessation support is offered at an initial consultation, with follow-up phone calls at 1 week and 1 month from the initial consultation, as appropriate.
6. Referrals to other professionals: Additional evidence-based risk reduction referrals (e.g. dietitian, sleep clinic) will be made by the practice nurse in consultation with the GP.

The intervention model of care will be coordinated by the practice nurse at each clinic under the supervision of each participant’s GP. Following real-world practice, consenting patients will be referred by the GP, at their discretion, to HomeBase and HMR. The written action plan will be implemented subsequent to HMR, but the order of HMR and HomeBase is dependent on patient and provider availability/convenience.
Intervention code [1] 323512 0
Treatment: Drugs
Intervention code [2] 323513 0
Treatment: Other
Intervention code [3] 323514 0
Rehabilitation
Comparator / control treatment
After baseline interview and spirometry, control group participants will be given a booklet on COPD from the Lung Foundation of Australia (LFA) and continue to receive usual care. The attending GP will determine the patient’s medication and follow-up as per normal practice.
Control group
Active

Outcomes
Primary outcome [1] 331263 0
Primary Outcome 1: Change in Health-related Quality of Life (HRQoL) assessed using St George’s Respiratory Questionnaire (SGRQ)

Timepoint [1] 331263 0
Timepoint: at 6 months from baseline
Secondary outcome [1] 409352 0
Secondary outcome 1: change in frequency of respiratory acute hospital visits (combined number of COPD admissions and ED visits) assessed via each State data linkage centres and/or participant self-report
Timepoint [1] 409352 0
Timepoint: at 6 & 12 months from baseline
Secondary outcome [2] 409353 0
Secondary Outcome 2: change in frequency of COPD-related unplanned GP visits assessed via linkage to the Medicare Benefits Schedule (MBS) and/or participant self-report
Timepoint [2] 409353 0
Timepoint: at 6 & 12 months from baseline
Secondary outcome [3] 409354 0
Secondary outcome 3: change in frequency of ‘all cause’ hospitalisations and ED visits assessed via each State data linkage centres and/or participant self-report
Timepoint [3] 409354 0
Timepoint: at 6 & 12 months from baseline
Secondary outcome [4] 409355 0
Secondary outcome 4: time to first event (hospitalisation, first ED visit, or death, whichever comes first) assessed via each State data linkage centres and/or participant self-report
Timepoint [4] 409355 0
Timepoint: at 6 & 12 months from baseline
Secondary outcome [5] 409356 0
Secondary outcome 5: change in Health-related Quality of Life (HRQoL) assessed using St George’s Respiratory Questionnaire (SGRQ)

Timepoint [5] 409356 0
Timepoint: at 12 months from baseline
Secondary outcome [6] 409357 0
Secondary outcome 6: change in lung function via spirometry testing

Timepoint [6] 409357 0
Timepoint: at 12 months from baseline
Secondary outcome [7] 409358 0
Secondary outcome 7: change in frequency of self-reported minor exacerbations and reliever use

Timepoint [7] 409358 0
Timepoint: at 6 & 12 months from baseline
Secondary outcome [8] 409359 0
Secondary outcome 8: change in anxiety and depression scores on the Hospital Anxiety and Depression Scale

Timepoint [8] 409359 0
Timepoint: at 6 & 12 months from baseline

Eligibility
Key inclusion criteria
Community dwelling adults aged 18 years and above with a history of mild-severe COPD and with a history of at least one exacerbation in the previous 24 months (based on self-reported COPD-related hospitalisation or use of short course oral steroids and/or antibiotics) will be eligible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Those unable to provide informed consent e.g. cognitive impairment, unable to communicate in English, with difficulty following the intervention, with a terminal illness (anticipated survival <12 months), symptoms suggesting unstable heart disease, or contraindications to spirometry as per standard guidelines will be excluded.

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)
1. Recruitment of practices and practice staff: General practice clinics will be invited to participate in the study through advertisements and through our contacts in primary health networks (PHNs). From each practice, one or two practice nurses will be trained to deliver the intervention working in close collaboration with a GP. Practice nurses may be shared between clinics in the same region, if there is no nurse available at a recruited clinic. General information on practice staffing and services provided will be obtained from each practice using a standard data collection form.
2. Cluster Randomisation: Clinics will be block randomised to intervention (TERRACOTTA) or control (usual care). Randomisation at the practice level will avoid contamination i.e. the same practice managing both control and intervention patients. Centralised web-based randomisation will be performed by an independent statistician. All participants recruited from a clinic will receive the intervention/usual care depending on the allocation.
3. Recruitment of patient participants: One or two nurses at each practice/clinic will be trained and employed on this project. The nurse will search the GP database/records and identify potential candidates for telephone interview based on their age, medical and medication history and lifestyle (e.g. smoking). At the end of this interview, those eligible/interested will be given an appointment for a face-to-face interview at the clinic. Signage and pamphlets will also be used within clinics to encourage participation. Written informed consent will be sought by the nurse during the face-to-face meeting, after provision of study information and opportunities for any questions. Practice staff are also informed of the study and asked to prospectively refer patients who meet eligibility criteria.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Cluster Randomisation: Clinics will be block randomised to intervention (TERRACOTTA) or control (usual care). Randomisation at the practice level will avoid contamination i.e. the same practice managing both control and intervention patients. Centralised web-based randomisation will be performed by an independent statistician. All participants recruited from a clinic will receive the intervention/usual care depending on the allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size: Changes in SGRQ at 6 months from enrolment is the primary efficacy end point. The minimum clinically important difference (MCID) on the SGRQ is 4 points. A reduction in SGRQ is regarded as a positive outcome. To show an average difference of 5 points in SGRQ change between groups using a standard deviation of change in SGRQ of 13 points (as per RADICALS trial), 143 participants per group (90% power and p=0.05) will be needed. Adjusting for clustering by practice (intra-class correlation=0.01), for a two-group cluster RCT with average cluster size of 10, the required sample size is 156 per arm. Allowing for 20% drop out, recruitment will continue until 400 participants have entered the trial (i.e. 200 in each arm). Therefore, 40 primary care practices will be recruited and 20 each randomised to TERRACOTTA and control. From each practice, 10 patients with poorly controlled COPD will be recruited.
With 200 subjects in each group, this study will have 80% power to demonstrate a 30% change in mean cumulative number of acute respiratory healthcare visits at 12 months (2.5 vs 1.75) assuming a standard deviation of 2.5 with two-sided significance level of 0.05. A 0.25 absolute difference in the mean cumulative number of COPD-related acute care visits per participant between study groups is considered clinically meaningful. The difference of 30% in respiratory acute healthcare visits was chosen based on an earlier self-management trial.
Statistical Analyses: The mean change in SGRQ scores over 6 months in each treatment group will be estimated. Difference between groups and 95% confidence interval will be determined. Multivariable analyses will be performed using linear regression for normally distributed continuous outcomes, logistic regression for binary outcomes and Cox proportional hazards regression for time to event outcomes. All regression analyses will be adjusted for clustering, prognostic variables and potential confounders e.g. socio-demographics, comorbidities. All primary analyses will be conducted according to the intention to treat (ITT) principle. Per protocol analysis (PPA) will also be undertaken to provide a measure of reliability of the primary analyses. A statistical analysis plan detailing all planned analyses will be prepared and analyses will be performed with SAS software version 9.4 (SAS Institute, Cary, NC, USA).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2022
Actual
1/12/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
400
Accrual to date
183
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 311167 0
Commercial sector/Industry
Name [1] 311167 0
GSK Medicines Research Centre
Country [1] 311167 0
United Kingdom
Primary sponsor type
University
Name
Monash University
Address
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences
381 Royal Parade, Parkville, VIC 3052
Australia
Country
Australia
Secondary sponsor category [1] 312523 0
None
Name [1] 312523 0
Address [1] 312523 0
Country [1] 312523 0
Other collaborator category [1] 282277 0
University
Name [1] 282277 0
University of Newcastle
Address [1] 282277 0
University Drive, Callaghan, NSW 2308
Australia
Country [1] 282277 0
Australia
Other collaborator category [2] 282278 0
University
Name [2] 282278 0
Bond University
Address [2] 282278 0
14 University Drive (off Cottesloe Drive), Robina, QLD, 4226
Australia
Country [2] 282278 0
Australia
Other collaborator category [3] 282279 0
University
Name [3] 282279 0
University of Melbourne
Address [3] 282279 0
The University of Melbourne Grattan Street, Parkville,Victoria, 3010,
Australia
Country [3] 282279 0
Australia
Other collaborator category [4] 282280 0
Commercial sector/Industry
Name [4] 282280 0
Chandlers Hill Surgery
Address [4] 282280 0
194A Chandlers Hill Road, Happy Valley, SA, 5159
Australia
Country [4] 282280 0
Australia
Other collaborator category [5] 282281 0
Hospital
Name [5] 282281 0
Austin Health
Address [5] 282281 0
Clinical Education Unit
Austin Hospital
PO Box 5555 Heidelberg VIC 3084
Australia
Country [5] 282281 0
Australia
Other collaborator category [6] 282282 0
Government body
Name [6] 282282 0
Australian E Health Research Centre (CSIRO)
Address [6] 282282 0
Building 101, Clunies Ross Street, Black Mountain, ACT, 2601
Australia
Country [6] 282282 0
Australia
Other collaborator category [7] 282283 0
Government body
Name [7] 282283 0
North Western Primary Health Network (NWPHN)
Address [7] 282283 0
Level 1, 369 Royal Parade, Parkville, Vic, 3052
Australia
Country [7] 282283 0
Australia
Other collaborator category [8] 282284 0
Government body
Name [8] 282284 0
Australian Primary Health Care Nurses Association (APNA)
Address [8] 282284 0
Level 17, 350 Queen Street, Melbourne, VIC, 3000
Australia
Country [8] 282284 0
Australia
Other collaborator category [9] 282285 0
Charities/Societies/Foundations
Name [9] 282285 0
Lung Foundation Australia (LFA)
Address [9] 282285 0
Level 2, 11 Finchley Street, Milton QLD 4064
Australia
Country [9] 282285 0
Australia
Other collaborator category [10] 282286 0
Commercial sector/Industry
Name [10] 282286 0
GSK Pharmaceuticals and Vaccines
Address [10] 282286 0
Level 3, 436 Johnston Street, Abbotsford, Victoria, 3067
PO Box 18095, Melbourne, Victoria, 8003
Australia
Country [10] 282286 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310697 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 310697 0
Ethics committee country [1] 310697 0
Australia
Date submitted for ethics approval [1] 310697 0
01/11/2021
Approval date [1] 310697 0
04/04/2022
Ethics approval number [1] 310697 0
28062

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

Contacts
Principal investigator
Name 118550 0
Dr Johnson George
Address 118550 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences
Monash University (Parkville Campus)
381 Royal Parade, Parkville
VIC 3052
Country 118550 0
Australia
Phone 118550 0
+61 3 9903 9178
Fax 118550 0
+61 3 9903 9629
Email 118550 0
Johnson.George@monash.edu
Contact person for public queries
Name 118551 0
Johnson George
Address 118551 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences
Monash University (Parkville Campus)
381 Royal Parade, Parkville
VIC 3052
Country 118551 0
Australia
Phone 118551 0
+61 3 9903 9178
Fax 118551 0
+61 3 9903 9629
Email 118551 0
Johnson.George@monash.edu
Contact person for scientific queries
Name 118552 0
Johnson George
Address 118552 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences
Monash University (Parkville Campus)
381 Royal Parade, Parkville
VIC 3052
Country 118552 0
Australia
Phone 118552 0
+61 3 9903 9178
Fax 118552 0
+61 3 9903 9629
Email 118552 0
Johnson.George@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Unidentifiable RAW DATA be made accessible in a data repository.
When will data be available (start and end dates)?
Start date: After baseline interviews/data collection
End date: After 5 years
Available to whom?
Only the researchers involved in the study will have access to the data.
The participants may obtain a copy of the summary of the study findings when the research project is completed, by contacting Dr Johnson George.
A report summarising the findings will be submitted to each general practice at the end of the project. The results of this project will be published in peer reviewed journal.
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Access subject to approval by investigator team. Primary contact: Principal Investigator Dr Johnson George (E-mail: Johnson.George@monash.edu).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15933Study protocol    By contacting Dr Johnson George (E-mail: Johnson.G... [More Details]
15934Statistical analysis plan    By contacting Dr Johnson George (E-mail: Johnson.G... [More Details]
15935Informed consent form    By contacting Dr Johnson George (E-mail: Johnson.G... [More Details]
15936Ethical approval    By contacting Dr Johnson George (E-mail: Johnson.G... [More Details]



Results publications and other study-related documents

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