Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000617864
Ethics application status
Approved
Date submitted
7/01/2021
Date registered
24/05/2021
Date last updated
21/01/2024
Date data sharing statement initially provided
24/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Preoperative exercise and education for patients undergoing major abdominal cancer surgery: A multicentre randomised controlled trial (PRIORITY Trial)
Scientific title
Effect of preoperative exercise and education on hospital complications in the primary admission for patients undergoing major abdominal cancer surgery: A multicentre randomised controlled trial (PRIORITY Trial)
Secondary ID [1] 303015 0
Nil Known
Universal Trial Number (UTN)
U1111-1262-8491
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced gastrointestinal cancers 320080 0
Recurrent gastrointestinal cancers 320484 0
Abdominal cancers 320485 0
Condition category
Condition code
Cancer 318010 318010 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 318018 318018 0 0
Pancreatic
Cancer 318019 318019 0 0
Liver
Cancer 318020 318020 0 0
Oesophageal (gullet)
Cancer 318021 318021 0 0
Stomach
Cancer 318022 318022 0 0
Bowel - Anal
Cancer 318377 318377 0 0
Bowel - Small bowel (duodenum and ileum)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The program will be delivered by trained clinicians in existing community facilities (e.g. physiotherapists or exercise physiologists close to participant home). We have deliberately chosen to position the study in a real world setting to ensure that the results will reflect what could be readily achieved in Australia and be more rapidly translated into clinical practice. Participants will be allocated to an individualised progressive preoperative exercise and education program (intervention group) or usual care alone (control group). All patients will undergo a baseline assessment prior to being randomised into either the preoperative exercise and education program (intervention) or usual care (control), and assessment week prior to surgery. The baseline and week before surgery assessments will collect subjective data with a self-reported questionnaire (measuring Duke Activity Status Index (DASI), Quality of life (SF-36v2), Physical Activity Questionnaire, Numerical Pain Rating Scale (NPRS) and Fatigue Severity Scale (FSS) and objective data with an assessment (includes a cardiorespiratory exercise test (CPET), a five times sit to stand test (5TSTS) and six minute walk test (6MWT)), for approximately one hour. Due to pandemic restrictions at the participating centres, the 5TSTS test will be performed by a trained clinician via video call in patients own home. The CPET and 6MWT assessments will be restricted and not uniformly assessed to all participants.

Individualised preoperative exercise and education program (Intervention group)
The main aim of the exercise program is to increase aerobic capacity and peripheral muscle endurance, muscle strength and respiratory muscle function and to educate participants to perform the exercise at home and about the surgical process. The individualised exercise program will follow the FITT-VP (frequency, intensity, time, type, volume and progression) principle suggested by the American College of Sports Medicine and will be delivered using three main components:

1) Supervised, individualised, progressive exercise program: The exercise program will consist of a 50-min individualised (one-to-one) training session with a physiotherapist or exercise physiologist, three times a week, for 4 to 8 weeks (range from 12 to 24 sessions). The exercise program will be tailored to each patient based on a health assessment, taking into consideration patients’ current health status, physical activity level, presence of co-morbidities and medical history. Each session will include warm-up (walking, cycling), aerobic/anaerobic exercises (cycle ergometer, treadmill, rowing machine, marching or running on the spot), resistance exercises (squat, push-up, shoulder press, hamstring curls, dumb-bell deadlift, biceps curl and overhead triceps extension), respiratory exercises (Deep breathing, relaxed breathing huff and cough (ABCT)), and cool-down activities (triceps, lower back, hip flexors, quadriceps, hamstrings, calf muscles, light jogging, walking or stretching). The aerobic exercises will be based on the individuals rated perceived exertion (modified Borg Scale) and the resistance training will be performed at an intensity of 40% to 60% of the 1-repetition maximum.

2) Home exercises (4 times/week): Home-based functional exercises will be prescribed by the treating physiotherapist or exercise physiologist to increase aerobic capacity and respiratory muscle function, including exercises with resistance provided by bodyweight, including push ups, squats, step ups. On the days participants are not attending the one-on-one training session, they will be instructed to perform the exercises for 30 minutes at home.

3) Daily physical activity advice: In addition to home exercises, participants will be encouraged to walk continuously for at least 30 minutes daily using an activity monitor. Participants will be asked to keep a daily diary of the number of steps per day and number of home exercises performed during the entire preoperative period. Step count will be extracted from the activity monitor daily by the participant, and all activity monitor data will be checked by the research team once the device has been returned. The access to this information will be limited to you and the research team. Once participation have been completed, the research team will delete all data from the activity monitor. The information stored on the activity monitor will be erased completely. No one, apart from the study investigators will have access to the data collected. No data collected from the activity monitor will be sent to any of the involved institutions. The results from the study will not be used to register the activity monitor.

The preoperative exercise program is 4-8 weeks, leading up to a week prior to the patients' surgery and includes:
- Up to 24 sessions x 50 minutes: Supervised, high-intensity training. Individualised exercise prescription, progression and follow-up with local physiotherapist or exercise physiologist either face-to-face or via tele-health.
- Up to 24 sessions x 30 minutes: Unsupervised home exercise.
- Up to 56 walking sessions x 30 minutes: Advice to walk continuously (30 minutes daily).

Treatment will be administered by local registered physiotherapists or exercise physiologists who will educate and provide high-intensity interval training, home exercises prescription and progression and physical activity advice in accordance with the study protocol. The adherence to the exercise program will be encouraged by the treating physiotherapist or exercise physiologist and by a team member that will message and/or call patients to check their compliance (i.e. log book).
Intervention code [1] 319302 0
Rehabilitation
Comparator / control treatment
Usual care (control) group
All participants involved in the trial will be recruited 4-8 weeks prior to surgery, will undergo a baseline assessment prior to being randomised, and an assessment week prior to surgery. Participants allocated to the control group will receive usual care consisted of nutritional counselling and advice on smoking cessation and reduction of alcohol intake, delivered by the surgeon and in preadmission clinic (CNC, dietician) as per standard preoperative care. No exercise advice will be provided and patients will be instructed to maintain their normal daily activities.

To measure their objective level of physical activity during the preoperative period, participants will be given an activity monitor in the week prior to their second assessment. Participants in the usual care (control group) will be asked to maintain their normal activities during this period. All feedback and incentivising features will be deactivated. Once the activity monitor is returned, the research team will erase the data completely from the activity monitor. The baseline and week before surgery assessments, completed by all participants, will collect subjective data with a self-reported questionnaire (measuring Duke Activity Status Index (DASI), Quality of life (SF-36v2), Physical Activity Questionnaire, Numerical Pain Rating Scale (NPRS) and Fatigue Severity Scale (FSS)) and objective data with an assessment (includes a CPET, 5TSTS and 6MWT). The 5TSTS will be performed one-on-one with physiotherapists either face-to-face at the study sites or via tele-health. Duration of the assessments is approximately one hour. Due to pandemic restrictions, CPET and 6MWT assessment are restricted and not uniformly available to all patients.
Control group
Active

Outcomes
Primary outcome [1] 326005 0
The primary outcome will be the proportion of participants developing in-hospital complications within the primary admission of the index surgery. The primary outcome will be independently extracted from the hospital electronic medical records by two trial personnel blinded to group allocation. Disagreements will be resolved by discussion.

Examples of potential in hospital complications include respiratory complications (e.g. pneumonia, lobar atelectasis, pleural fluid or respiratory failure), infectious complications (e.g. wound infection, surgical site infection or sepsis), cardiovascular complications (heart failure, acute myocardial infarction or deep venous thrombosis), renal complications (e.g. acute kidney injury or urinary retention), hepatic, pancreatic gastrointestinal complications (e.g. pancreatitis or gastrointestinal haemorrhage), surgical complication (e.g. anastomotic leak, urinary tract injury or mechanical bowel obstruction), neurological deficit or haematological complication, wound complication, or pain.
Timepoint [1] 326005 0
In hospital complication data will be extracted whilst each patient is admitted in hospital.
Secondary outcome [1] 389840 0
Intensive care unit and hospital length of stay (composite outcome). This information will be extracted from the hospital electronic medical records.
Timepoint [1] 389840 0
Measured by duration of stay on the intensive care unit and hospital stay (in days); with the day of the index surgery considered as day 0. Measured upon patient discharge from intensive care unit and upon discharge from hospital.
Secondary outcome [2] 389848 0
Patient's quality of life. The QualityMetric Health Outcomes Scoring Software will be used to obtain the final scores of the eight quality life domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) and the two physical and mental summary scores.
Timepoint [2] 389848 0
Measured by the Short Form 36 version 2 at baseline (4-8 weeks preoperative), within the week before surgery, day of discharge and 3 months postoperative.
Secondary outcome [3] 389849 0
Investigations on postoperative morbidity will be conducted as a secondary outcome measure. 5 days postoperative morbidity will be assessed by the Postoperative Morbidity Survey (POMS) and 30 days postoperative morbidity will be captured using the postoperative complication definition recommended by the StEP-COMPAQ group. The severity of each complication will be grade using the Clavien-Dindo. Days alive and at home within first 30 days after surgery (DAH-30)
Timepoint [3] 389849 0
5 days (or the day of discharge if patient is discharged earlier) and 30 days post-operative morbidity.
Secondary outcome [4] 389859 0
Health resource use (costs) and productive losses (composite outcome). Information on patient out of pocket and health system resource use (in Australian dollars, AUD), including the cost of the intervention will be collected, via follow-up questionnaire designed specifically for the study. Information about the impact of the intervention and surgery on return to work, and leisure activities will be used to inform productive losses.
Timepoint [4] 389859 0
Health resource use (costs) and productive losses will be collected from randomisation up to 3 months postoperative (i.e. baseline, week prior to surgery, discharge and 3 months postoperative).
Secondary outcome [5] 395840 0
Functional capacity (exploratory outcome) will be measured by the Cardiopulmonary Exercise Test (CPET). Positive changes in CPET parameters occurring between baseline and within a week before surgery will be defined as success of the intervention. Due to pandemic restrictions, CPET-derived functional capacity will not be collected for some patients.,
Timepoint [5] 395840 0
Measured between baseline (4-8 weeks postoperative) and within a week before surgery.
Secondary outcome [6] 395841 0
Self reported physical activity (exploratory outcome) will be measured through questionnaires using The Active Australia Survey, strength questions from the New South Wales Health population survey and sitting questions from the International Physical Activity Questionnaire short form (IPAQ-SF).
Timepoint [6] 395841 0
Measured at baseline, within a week before surgery, day of discharge and 3 months postoperative.
Secondary outcome [7] 395842 0
Objective Physical Activity (exploratory outcome) will be measured using an activity monitor.
Timepoint [7] 395842 0
Measured during the preoperative period. For the intervention group the activity monitor will be used during the whole intervention period and will provide real-time visual feedback. For the control group, objective physical activity will be collected using an activity monitor without any visual feedback during the 7 days prior to their second assessment (within week prior to scheduled surgery).
Secondary outcome [8] 395843 0
Pain Intensity (exploratory outcome) will be measured on a 0 to 10 (higher scores indicate worst symptoms) numerical pain rating scale (NPRS).
Timepoint [8] 395843 0
Measured at baseline, within a week before surgery, discharge day, and 3 months postoperative.
Secondary outcome [9] 395844 0
Satisfaction (exploratory outcome) will be measured via a self-reported question, designed specifically for the study.
Timepoint [9] 395844 0
Measured at week before surgery.
Secondary outcome [10] 395845 0
Fatigue (exploratory outcome) will be measured using the Fatigue Severity Scale.
Timepoint [10] 395845 0
Measured at baseline, within a week before surgery, discharge day, and 3 months postoperative.
Secondary outcome [11] 395846 0
Adverse events (exploratory outcome) are considered any undesirable event, such as injury, fall, severe breathlessness, new or progressive pain and progressive fatigue. Adverse events will be measured via a self-reported questionnaire.
Timepoint [11] 395846 0
Adverse events will be collected during the preoperative period. In case of serious adverse events the trial chief investigator and trial research officer are notified immediately, participants are managed appropriately and the incident is reported to the relevant hospital ethics committee.
Secondary outcome [12] 395847 0
Five times sit to stand test (exploratory outcome). Lower limb strength and function will be measured using the five times sit to stand test (5TSTS). Due to pandemic restrictions, the 5TSTS will be performed by a clinician via video call in patients own home.
Timepoint [12] 395847 0
Five times sit to stand test will be conducted preoperatively at baseline and week prior to surgery.
Secondary outcome [13] 395848 0
6 minute walk test (exploratory outcome). Aerobic capacity and endurance will be measured using the six minute walk test (6MWT). The test will be performed using the American Thoracic Society (ATS) guidelines. Due to pandemic restrictions, 6MWT will not be collected for some patients.
Timepoint [13] 395848 0
6 minute walk test will be conducted preoperatively at baseline and week prior to surgery.
Secondary outcome [14] 395849 0
Adherence to the study exercise program (exploratory outcome) defined as the percentage of exercise sessions attended/performed by those randomised to the intervention group, will be reported using the clinician activity record and patient exercise diary.
Timepoint [14] 395849 0
Adherence to the study exercise program will be collected during the preoperative period. Participants will be contacted on a weekly basis to report their adherence to the preoperative program.
Secondary outcome [15] 395852 0
Treatment and Health Services (exploratory outcome) will include information about treatments (physiotherapy, etc), diagnostic imaging, visiting GP/specialist. Treatment and Health Services measured up to 3 months.
Timepoint [15] 395852 0
Treatment and Health Services will be collected via follow-up questionnaire for the cost-effective analysis.
Secondary outcome [16] 406038 0
Duke Activity Status Index (DASI) will be measured through a 12-item scale in the form of a self-reported questionnaire. The final score ranges from 0 to 58, where a higher score indicates high functional capacity.
Timepoint [16] 406038 0
Measured at baseline and within a week before surgery.

Eligibility
Key inclusion criteria
To be eligible for the study, patients will be adults aged 18-80 years:
- Undergoing elective major surgery for advanced or recurrent gastrointestinal cancer (i.e. pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy);
- Consult a gastrointestinal surgeon at least 4 weeks prior to planned surgery.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from the study if they have:
- Cognitive impairment such that they are unable to provide informed consent;
- Co-morbidity preventing participation in exercise and physical assessments (i.e. cardiorespiratory, musculoskeletal, neurological);
- Presenting with very poor functional capacity – Defined as a score of ‘zero’ (i.e. No) to all the following Duke Activity Status Index (DASI) (known collectively as the M-DASI-AQ): 1) Can you climb a flight of stairs or walk up a hill?; 2) Can you do heavy work around the house?; 3) Can you do yard work?; and 4) Can you participate in strenuous sports?;
- Inadequate English language to complete outcome measures;
- Currently participating in an exercise program.

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)
The randomisation sequence will be prepared a priori using a central secure randomisation service to ensure concealment of treatment allocation. Central secure randomisation service is completed by computer. A randomisation module will be created by the trial's statistican and uploaded by an independent Research Officer not involved in the trial, into the Research Electronic Data Capture (REDCap) database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1:1 allocation ratio in random permuted blocks of sizes 4 or 2 stratified by hospital, to ensure balance in treatment assignment within hospital
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
The study is also a multi-centre, pragmatic, comparative randomised controlled trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
To achieve the primary aim of the study, 172 participants will provide 90% power to detect a difference of 25% in complication rates between the intervention and control groups. This difference was considered clinically meaningful by our clinical and consumer panel. These calculations were based upon the overall complication rate being 50% in the control groups, based on our current clinical experience, allowing for up to 5% loss to follow-up and a two-side alpha of 0.05. The 5% loss to follow-up was estimated from our previous prospective clinical trials. Sample size calculations have been conducted using PASS15 software.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/11/2021
Actual
19/11/2021
Date of last participant enrolment
Anticipated
1/07/2024
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
210
Accrual to date
200
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 18209 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 18210 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 32269 0
2050 - Camperdown
Recruitment postcode(s) [2] 32270 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 307426 0
Government body
Name [1] 307426 0
National Health and Medical Research Council (NHMRC)
Country [1] 307426 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Level 3, F23 Administration building, The University of Sydney, Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 308095 0
None
Name [1] 308095 0
Address [1] 308095 0
Country [1] 308095 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307508 0
Sydney Local Health District Human Research Ethics Committee - CRGH
Ethics committee address [1] 307508 0
Ethics committee country [1] 307508 0
Australia
Date submitted for ethics approval [1] 307508 0
Approval date [1] 307508 0
19/03/2020
Ethics approval number [1] 307508 0

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

Contacts
Principal investigator
Name 107486 0
A/Prof Daniel Steffens
Address 107486 0
Surgical Outcomes Research Centre, Royal Prince Alfred Hospital
PO Box M157 Missenden Road, Sydney, NSW 2050 Australia
Country 107486 0
Australia
Phone 107486 0
+61295153202
Fax 107486 0
Email 107486 0
[email protected]
Contact person for public queries
Name 107487 0
Daniel Steffens
Address 107487 0
Surgical Outcomes Research Centre, Royal Prince Alfred Hospital
PO Box M157 Missenden Road, Sydney, NSW 2050 Australia
Country 107487 0
Australia
Phone 107487 0
+61295153202
Fax 107487 0
Email 107487 0
[email protected]
Contact person for scientific queries
Name 107488 0
Daniel Steffens
Address 107488 0
Surgical Outcomes Research Centre, Royal Prince Alfred Hospital
PO Box M157 Missenden Road, Sydney, NSW 2050 Australia
Country 107488 0
Australia
Phone 107488 0
+61295153202
Fax 107488 0
Email 107488 0
[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


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
SourceTitleYear of PublicationDOI
EmbasePRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL).2022https://dx.doi.org/10.1186/s12885-022-09492-6
EmbaseImproving outcomes in patients with oesophageal cancer.2023https://dx.doi.org/10.1038/s41571-023-00757-y
N.B. These documents automatically identified may not have been verified by the study sponsor.