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Trial registered on ANZCTR


Registration number
ACTRN12619000214134
Ethics application status
Approved
Date submitted
24/01/2019
Date registered
14/02/2019
Date last updated
2/11/2021
Date data sharing statement initially provided
14/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Preoperative exercise therapy for patients with cancer: A randomised-controlled trial
Scientific title
Feasibility and effectiveness of preoperative exercise therapy for patients with cancer in the Grampians region of Victoria: A randomised-controlled trial
Secondary ID [1] 297154 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
The PROTECT Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 311208 0
Colorectal Cancer 311209 0
Breast Cancer 311210 0
Condition category
Condition code
Cancer 309831 309831 0 0
Breast
Cancer 309832 309832 0 0
Prostate
Cancer 309833 309833 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 1 Randomised-controlled trial. Following the completion of written informed consent, participants will be stratified (by cancer type) and randomised (1:1) to one of two groups consisting of: a) the prehabilitation intervention group or b) usual care group.

The intervention will consist of a supervised exercise training session by an accredited exercise physiologist once every three days (estimated four weeks) up and until 3-5 days before surgery in a gym setting. If the scheduled date for surgery is > 4 weeks, or is delayed, participants will continue attending supervised exercise training sessions as per the protocol. Each exercise training session will commence and conclude with a 5-minute warm up and cool-down on a self-selected apparatus (treadmill; stationary bicycle; cross-trainer) and can be conducted in a group or individually. All training will be Aerobic and will be conducted predominantly on a cycle ergometer with additional aerobic exercises (e.g. treadmill, step-ups, cross-trainer) will also be used to maintain participant engagement with the program. The prescribed intensity will be set at 40-70% of HRR and/or a rating of perceived exertion of 11-16 (“fairly light” to “hard”; 6 – 20 scale). Exercise training sessions last between 45-60 minutes, which will aim to include approximately 30 minutes of dedicated aerobic training.

The Accredited Exercise Physiologist who is training the participants may make amendments to the training protocol on an individual basis. However, the exercise sessions will be delivered in a group setting based on particpants availbility. This will allow potential adjustments to the exercise type, intensity and volume during the session based on the patient’s perceived exertion. All amendments must be recorded.

Physical assessments will be performed pre-intervention, Post-exercise intervention completion (approximately 48 hrs pre-surgery), and at 30 days following surgery. Peri- and post-operative outcomes will be collected for all participants. Following the 30-day post-operative testing time-point, both groups will be invited to receive four weeks of biweekly supervised exercise training.

Missed sessions should aim to be rescheduled within the same week, if possible, while allowing at least 48 hours between exercise sessions. The total number of supervised exercise sessions should not exceed three per week. Attendance will be defined as the number of in-person exercise sessions divided by the number of planned in-person sessions. If any sessions are missed, the number and reasons should be recorded. Every attempt should be made to reschedule missed sessions.
Intervention code [1] 313434 0
Prevention
Intervention code [2] 313483 0
Lifestyle
Comparator / control treatment
The usual care group will comply with normal BHS procedures. There is no current prehabilitation approach employed at Ballarat Health Services. At present, patients have an initial assessment that include outcome measures (6MWT and then depending on their current status potentially Upper Limb or Lower Limb strength tests, balance, questionnaires). Patients will then be booked in to 1-2 group sessions per week in conjunction with a HEP or just a HEP if they can’t attend supervised sessions. The primary focus is to increase cardiovascular fitness with the addition of strength based exercises to assist with improving function. This will then continue up until surgery/treatment date.
Control group
Active

Outcomes
Primary outcome [1] 318792 0
To examine the effectiveness of pre-operative exercise training (‘prehabilitation’) to induce clinically relevant improvements in physical fitness (cardiopulmonary function) in patients with prostate, colorectal and breast cancer undergoing surgery in the Grampians region of Victoria.


Assessed by number of adverse events and patient compliance. For example adverse clinical or laboratory findings, illness, or exacerbation/progression of disease/condition from the baseline assessment. All adverse events will be assessed by the prinicipal researcher present and a health professional present. An adverse event will be recorded on a AE/SAE report form and the PI responsible will present the AE to the HREC.

This is a composite outcome.
Timepoint [1] 318792 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Primary outcome [2] 318876 0
To examine the feasibility of pre-operative exercise training (‘prehabilitation’) to induce clinically relevant improvements in physical fitness (cardiopulmonary function) in patients with prostate, colorectal and breast cancer undergoing surgery in the Grampians region of Victoria. The outcome of ventilatory threshold will be assessed through a metabolic cart.


Assessed by changes in ventilatory threshold (VT)
Timepoint [2] 318876 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [1] 366051 0
To compare changes in resting health characteristics between the intervention and usual care groups.

Assessed by Body Mass, Height and Resting vital signs. Stadiometer, digital scales and a sphygmomanometer will be used to assess the above characteristics.

This is a composite outcome.
Timepoint [1] 366051 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [2] 366304 0
To determine the effect of prehabilitation on self-reported determinants of physical well-being.


Assessed by FACT questionnaires (FACT-P, FACT - C, FACT - Br and FACIT-F) and by accelerometers
Timepoint [2] 366304 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [3] 366305 0
To compare changes in large artery compliance parameters between the intervention and usual care groups.

Assessed by SphygmoCor device (AtCor Medical, Sydney, Australia) to derive pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (cf-PWV).
Timepoint [3] 366305 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [4] 366306 0
To compare changes in cardiopulmonary exercise testing variables between the intervention and usual care groups.

Assessed by submaximal cardiopulmonary exercise test (CPET) will be performed on an electronically-braked cycle ergometer. CPET variables tested will include Vo2Max and VT.
Timepoint [4] 366306 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [5] 366307 0
To examine the effect of prehabilitation on inflammatory and immunity (blood) biomarkers compared with matched control group. Antigens will include distinguishing markers of the main immune subsets (CD4, CD8, CD25, CD45RA/RO, CD56, CD62), markers of activation (CD69, CD122, CD127, CD161, perforin, FasL, NK and chemokine receptors), as well as other antigens used to distinguish and characterize particular immune cells. Inflammation markers will include CRP.

This is a composite outcome.


Assessed by fasted blood draws by an experienced practitioner
Timepoint [5] 366307 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [6] 366308 0
To examine the effects of prehabilitation to impact post-operative (30 day follow-up) health outcomes.

Will be extrapolated by the principal investigators (MW, DH, SB) from electronic medical records. Body Mass, Height, Resting vital signs, fasted blood samples and any FACT questionnaires will be assessed.
Timepoint [6] 366308 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [7] 366588 0
To determine the effect of prehabilitation on self-reported determinants emotional well-being


Assessed by FACT questionnaires (FACT-P, FACT - C, FACT - Br and FACIT-F) and by accelerometers
Timepoint [7] 366588 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.
Secondary outcome [8] 366589 0
To determine the effect of prehabilitation on self-reported determinants health related quality of life.


Assessed by FACT questionnaires (FACT-P, FACT - C, FACT - Br and FACIT-F) and by accelerometers
Timepoint [8] 366589 0
Post- exercise intervention completion (approximately 48 hrs pre-surgery), and at 30-days following surgery.

Eligibility
Key inclusion criteria
Participant provides written informed consent

Scheduled for prostate, colorectal or breast cancer surgery

Age greater than or equal to 18 years

Medical clearance to undergo a symptom limited cardiopulmonary exercise test and supervised exercise training

ECOG status 0-1

Participant can attend exercise training venue to meet threshold of 80% compliance with supervised exercise program.

Participants must be able to understand and follow instructions in English
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Surgery scheduled in less than or equal to 2 weeks following diagnosis

Any absolute or relative contraindications to participate in exercise testing as described by the American College of Sports Medicine

Metastatic disease

Currently enrolled in an experimental treatment with non-approved drugs at the time of enrolment

Current congestive heart failure (New York Heart Association Class II, III or IV)

Recent serious cardiovascular events (less than or equal to 12 months) requiring hospitalisation

Uncontrolled infection, non-healing wound, bone fracture or cardiac disease that would make this protocol hazardous for the patient to participate

Psychiatric illness that would prevent informed consent or study protocol adherence

Any abnormality identified during the initial cardiopulmonary exercise test that indicates that it would be considered unsafe to participate in an exercise training intervention

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)
Randomisation will be completed via an online software application (Sealed Envelope Ltd. 2017. Simple randomisation service [Online] Available from: https://www.sealedenvelope.com/simple-randomiser/v1]).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). Block randomisation in random blocks of 2, 4 or 6 will be conducted by an individual external to the investigation.
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
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Primary and secondary outcomes analysed and presented using appropriate statistical procedures will be undertaken. Data will be tested for normality (of distribution) using a Shapiro-Wilks test. Random effects mixed modelling with Bonferroni post-hoc analyses will be used to compare mean changes in outcomes between groups at each assessment period, with time (pre-treatment, post-treatment, 30-day post-operative follow-up) and group allocation (intervention or usual care) as the fixed factors. A group by time interaction term will be used to formally test for differences between groups. Data will also be scrutinised for within-group differences. Multiple regression will be employed to determine the association between the change in measured physiological and psychosocial outcomes, and operative outcomes. Data analysis will be conducted using SPSS version 24.0 and Stata/IC general purpose statistical software. Analysis of biochemical samples will employ a principle component method (Factor analysis for mixed data), and multiple linear regression will be employed to compare continuous and phenotypic characteristics in each participant group. Descriptive statistics will be presented as group mean ± standard deviation (SD), or median (interquartile range) where appropriate. An alpha of P<0.05 will be used to denote statistical significance.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/10/2019
Actual
14/10/2019
Date of last participant enrolment
Anticipated
11/05/2020
Actual
11/08/2021
Date of last data collection
Anticipated
15/06/2020
Actual
30/09/2021
Sample size
Target
50
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12974 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment postcode(s) [1] 25453 0
3350 - Ballarat Central

Funding & Sponsors
Funding source category [1] 301708 0
Charities/Societies/Foundations
Name [1] 301708 0
Western Alliance Health Research Ltd
Country [1] 301708 0
Australia
Primary sponsor type
University
Name
Federation University Australia
Address
Federation University Australia, 1 University Drive, Mt Helen Campus, Ballarat, VIC Australia, 3353
Country
Australia
Secondary sponsor category [1] 301435 0
Hospital
Name [1] 301435 0
Ballarat Regional Intergrated Cancer Centre
Address [1] 301435 0
1 Drummond Street, North, Ballarat Victoria 3350
Country [1] 301435 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302427 0
Ballarat Health Services & St John of God Hospital Ballarat Human Research Ethics Committee
Ethics committee address [1] 302427 0
Ethics committee country [1] 302427 0
Australia
Date submitted for ethics approval [1] 302427 0
08/12/2018
Approval date [1] 302427 0
20/12/2018
Ethics approval number [1] 302427 0
HREC/46280/BHSSJOG-2018-160871(v4)

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

Contacts
Principal investigator
Name 90206 0
Prof Fergal Grace
Address 90206 0
Federation University Australia, Office P923, Building P, Mt Helen Campus, Ballarat VIC Australia, 3353
Country 90206 0
Australia
Phone 90206 0
+61353279441
Fax 90206 0
Email 90206 0
f.grace@federation.edu.au
Contact person for public queries
Name 90207 0
Stephen Brown
Address 90207 0
Ballarat Regional Integrated Cancer Centre (BRICC), 1 Drummond St N, Ballarat Central VIC 3350
Country 90207 0
Australia
Phone 90207 0
+61 03 5320 8500
Fax 90207 0
Email 90207 0
Stephen.brown@bhs.org.au
Contact person for scientific queries
Name 90208 0
Matthew Wallen
Address 90208 0
Federation University Australia, Office P919, Building P, Mt Helen Campus, Ballarat VIC Australia, 3353
Country 90208 0
Australia
Phone 90208 0
+61353279618
Fax 90208 0
Email 90208 0
m.wallen@federation.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  d.hennessy@federation.edu.au


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.