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Trial registered on ANZCTR


Registration number
ACTRN12620000496910
Ethics application status
Approved
Date submitted
11/03/2020
Date registered
20/04/2020
Date last updated
20/04/2020
Date data sharing statement initially provided
20/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Prehabilitation to Improve outcomes afteR Autologous sTem cEll transplantation (PIRATE) – A randomised controlled trial

Scientific title
Prehabilitation to Improve outcomes afteR Autologous sTem cEll transplantation (PIRATE) – A randomised controlled trial

Secondary ID [1] 300769 0
None
Universal Trial Number (UTN)
U1111-1249-5528
Trial acronym
PIRATE
Linked study record
Not Applicable

Health condition
Health condition(s) or problem(s) studied:
Cancer 316617 0
Condition category
Condition code
Cancer 314847 314847 0 0
Myeloma
Cancer 314848 314848 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 314849 314849 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 314850 314850 0 0
Leukaemia - Acute leukaemia
Cancer 314851 314851 0 0
Leukaemia - Chronic leukaemia
Cancer 314852 314852 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Name of intervention: Prehabilitation - nutrition education and advice and exercise
Who will deliver the intervention: The intervention will be delivered by a physiotherapist and dietitian with experience treating people with cancer.

Mode of delivery: exercise - face to face, nutrition face to face and telephone

Dose: Participants randomised to the prehabilitation group will be offered a comprehensive physiotherapy assessment and twice weekly, 60-minute exercise classes for up to 8 weeks pre-transplant. All participants enrolled in the study will aim to complete 8 weeks of prehabilitation however it is possible they will receive a shorter period of prehabilitation dependent of timing of their stem cell transplant as some patients may not be notified if they are proceeding to transplant until 6 weeks prior.
The exercise intervention will be in a circuit format and consist of aerobic and resistance exercise, completed at a moderate intensity (4-6 BORG rating of perceived exertion (RPE) and/or 60-80% Heart rate (HR) maximum for aerobic exercises, 60-80% 1-repetition maximum (for pin-loaded machines or 10-12 repetition maximum (RM) for resistance exercise) in accordance with published guidelines. Exercise will be tailored to each patient following an assessment by the physiotherapist. Participants will complete a 5 minute warm up, aim to complete 25 minutes aerobic exercise, 20 minutes of resistance exercise, 5 minutes of flexibility or balance training (as indicated) and 5 minute cool down. Exercise intensity during aerobic exercise will be monitored by the physiotherapist using the modified BORG scale and using a portable heart rate monitor. During weeks one and two, participants will aim to work at a BORG RPE of 3 (moderate), and by week 8 participants will aim to work at a 5-6 (hard) on the scale. For resistance exercise, weights will be progressed once a participant is achieving 2 to 3 sets of 10-12 repetitions. Resistance exercise may include upper and lower body resistance exercise such as squats, step ups, free weights, wall push-ups, free weights, resistance exercise bands, pin-loaded machines (lat pull down, leg press, chest press). Estimated 1 RM testing will be reassessed at week 4 to ensure sufficient strength training stimulus. Aerobic exercise may include treadmill, stationary cycle, and arm ergometer. Various upper and lower body stretches and balance exercise will also be incorporated into the program as required. Participants in the prehabilitation group will be encouraged to complete an additional 30-minute aerobic exercise training session at home to comply with exercise guidelines for people with cancer. Readily available written instructions with guidelines for exercise after cancer readily available from the American College of Sports Medicine will also be given. Patients will be instructed to remain as active as possible and avoid prolonged periods of sitting and lying in the period following stem cell transplant.

Patients will also receive a comprehensive, 60 minute face to face nutrition assessment with a dietitian. The nutrition assessment will comprise review of patients energy intake, food group adequacy and malnutrition screening. The dietitian will provide written information handouts readily available from the Peter Macallum Cancer Centre and fortnightly phone calls including education about weight management, protein intake and dietary balance over the 8 weeks (up to 4 sessions).

Location/timing: Box Hill Hospital prior to autologous stem cell transplantation

Procedures and Personalisation: Exercise will be tailored to each patient following an assessment by the physiotherapist in accordance with guidelines from the American College of Sports Medicine 2019. Patients will be offered tailored dietary education and advice based on their assessment results with the dietitian.
Intervention code [1] 317094 0
Rehabilitation
Intervention code [2] 317149 0
Treatment: Other
Intervention code [3] 317150 0
Lifestyle
Comparator / control treatment
Name of comparator: Physiotherapy assessment and standardised written exercise advice from the American College of Sports Medicine provided prior to autologous stem cell transplantation. Participants will continue to receive their usual medical care.

Who will deliver comparator: Registered physiotherapist with oncology experience

Dose: one 60 minute session

Location/timing: Box Hill hospital prior to autologous stem cell transplantation

Procedures and personalisation: Standardized written exercise advice from the American College of Sports Medicine will be given to patients as this is an issue for all people with cancer. Standard written advice has previously been applied as a control in exercise oncology trials.
Control group
Active

Outcomes
Primary outcome [1] 323197 0
Physical capacity assessed using 6 minute walk test
Timepoint [1] 323197 0
Baseline, week 8, and 1 month post transplant (Week 13)(primary end point) after randomisation
Secondary outcome [1] 381144 0
Objective physical activity (Daily time spent walking, Daily time spent in moderate to vigorous activity, Daily steps, Daily time sitting or lying) assessed using accelerometer-based activity monitor (ActivPal)
Timepoint [1] 381144 0
Baseline, Week 8 and 13 after randomisation
Secondary outcome [2] 381146 0
Inflammation assessed by measuring C-Reactive protein from venous blood samples
Timepoint [2] 381146 0
Baseline, Week 8, and Week 13, after randomisation
Secondary outcome [3] 381147 0
Health related quality of life using the European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC-QLQ C30) and HDC-29 supplement
Timepoint [3] 381147 0
Baseline, week 8, and week 13, after randomisation
Secondary outcome [4] 381148 0
Self efficacy for physical activity measured using a 7 item questionnaire adapted from the Health Action Process Approach
Timepoint [4] 381148 0
Baseline, week 8, and week 13 after randomisation
Secondary outcome [5] 381149 0
Nutritional status will be measured using the Patient-Generated Subjective Global Assessment (PG-SGA)
Timepoint [5] 381149 0
Baseline, week 8 , and week 13 after randomisation
Secondary outcome [6] 381150 0
Handgrip strength assessed using a handgrip dynamometer (Jamar®, Patterson Medical, IL, USA)
Timepoint [6] 381150 0
baseline, week 8 , and week 13 after randomisation
Secondary outcome [7] 381151 0
Time to stem cell engraftment calculated by number of days from transplant to engraftment. Engraftment is defined as neutrophils >0.5 x 109/L for three days without support and platelets >50 x 109/L for five days without transfusion. This will be collected from the medical record.
Timepoint [7] 381151 0
between week 8 and 13 after randomisation
Secondary outcome [8] 381152 0
Hospital length of stay
Days that the patient is in the hospital from day of stem cell infusion to day of discharge
This will be collected from routinely collected hospital data
Timepoint [8] 381152 0
Between week 8 and 13 after randomisation
Secondary outcome [9] 381153 0
Number of emergency department presentations over three months after discharge from the AutoSCT admission.
Timepoint [9] 381153 0
3 months post hospital discharge (approximately week 25 after randomisation). This will be collected using routinely collected hospital data
Secondary outcome [10] 381155 0
Number of hospital readmissions over 3 months after discharge from the Auto SCT admission and associated inpatient days with each readmission. This will be assessed using routinely collected hospital data.
Timepoint [10] 381155 0
3 months post hospital discharge (approximately week 25 after randomisation)
Secondary outcome [11] 381488 0
Number of adverse events defined by the World Health Organization and reasons for non-participation. These will be assessed using participant self-report and access to medical records. Adverse events will be categorised as minor adverse events or serious adverse events. A minor adverse event is defined as an incident that occurs while the person is participating in the intervention that results in no injury or minor injury (e.g. fatigue, exacerbation of pre-existing musculoskeletal pain) that requires none or minor medical intervention. A serious adverse event is defined as an incident that occurs while the person is participating in the intervention that results in death, serious injury or re-hospitalisation. Complications related to the stem cell transplant procedure will be included in adverse event reporting for each group (e.g. infection, bleeding, mucositis, parental nutrition requirements, intensive care support).
Timepoint [11] 381488 0
Week 8 and Week 13 after randomisation
Secondary outcome [12] 381489 0
Number of Symptom and Urgent Review Clinic (SURC) presentations over three months after discharge from the AutoSCT admission.
Timepoint [12] 381489 0
3 months post hospital discharge (approximately week 25 after randomisation)
This will be collected using patient medical records
Secondary outcome [13] 381821 0
Reasons for non-participation in an exercise session or non-completion of the program unrelated to adverse events (e.g. parking, work commitments). These will be recorded using a standardised work sheet developed by the researchers
Timepoint [13] 381821 0
Week 8

Eligibility
Key inclusion criteria
Participants recruited from haematology clinics at Eastern Health and affilitated haematology private practices where patients will be referred to Eastern Health for Auto SCT. Participants will be eligible if they: are aged 18 years and over; have a haematological malignancy and are waitlisted for autologous stem cell transplant; and are able to give written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if patients have a medical condition that contraindicates participation in an exercise-based rehabilitation program as assessed by a physiotherapist or medical practitioner.
• They have an Australian-modified Karnofsky Performance status of <60 or ECOG >2.
• They have a cognitive impairment that precludes their ability to provide written, informed consent as assessed by their treating clinician.

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)
Assignments will be placed in sequentially numbered, opaque, sealed envelopes prior to study commencement by an independent researcher with no role in subject recruitment or administration of trial interventions.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be allocated to the prehabilitation group or control group according to an online computer generated randomisation program, www.randomization.com using permuted blocks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
To gain a preliminary understanding of the effect of the intervention on clinical outcomes, a sample size sufficient to detect a clinically significant between-group difference in physical capacity of 53 m, assuming a large effect size of 1.3 at a power of 0.8 and an alpha level of 0.05, will be sought. It was calculated a sample of 22 patients waitlisted for Auto SCT at Eastern Health would be adequate. No minimal clinically significant difference has been calculated in patients receiving Auto SCT therefore it was estimated to be 41 m based on half a standard deviation of scores of a mixed cohort of cancer survivors.
Approximately 30 people are treated with ASCT at Eastern Health each year. Our sample size represents a recruitment rate of 75% which is similar to a recently completed cancer rehabilitation trial at Eastern Health. It is anticipated there will be high acceptance of the trial given the lack of existing allied health support for this cohort at Eastern Health. Our scoping study in 2017 highlighted desire from patients to have access to rehabilitation early after cancer diagnosis through programs located onsite at Box Hill Hospital.

The primary outcome (physical capacity at 1 month post-transplant) will be analysed using linear mixed effects models. Modelling will account for variation in baseline values. This method accounts for within-participant dependence of observations over time, and for missing data, allowing some participants to have missing observations at certain time points. If more than 5% of data are missing, a multiple imputation process will be used, providing the assumption data are missing at random is met. A similar approach will be used for analysis of secondary outcomes collected longitudinally. The time spent in moderate to vigorous physical activity will be estimated using a cut-off of 100 steps/minute for moderate intensity physical activity. The proportion of participants meeting physical activity guidelines will be described. The number of emergency department, SURC presentations and hospital admissions will be reported as an incidence rate ratio using a negative binomial regression model. To avoid bias and to maximize the randomisation process, all available data will be analysed according to allocation (intention to treat analysis), regardless of compliance.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16110 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 29626 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 305226 0
Charities/Societies/Foundations
Name [1] 305226 0
Eastern Health Foundation
Address [1] 305226 0
8 Arnold St , Box Hill
Victoria 3128
Country [1] 305226 0
Australia
Primary sponsor type
Hospital
Name
Eastern Health
Address
Level 2, 5 Arnold St, Box Hill
Victoria 3128
Country
Australia
Secondary sponsor category [1] 305584 0
None
Name [1] 305584 0
Address [1] 305584 0
Country [1] 305584 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305573 0
Eastern Health Human Research Ethics Committee
Ethics committee address [1] 305573 0
Level 2, 5 Arnold St, Box Hill
Victoria 3128
Ethics committee country [1] 305573 0
Australia
Date submitted for ethics approval [1] 305573 0
20/02/2020
Approval date [1] 305573 0
11/03/2020
Ethics approval number [1] 305573 0
E 20/003/61055

Summary
Brief summary
The purpose of this study is to see if providing rehabilitation (prehabilitation) before stem cell transplant builds physical strength and fitness.

Who is it for?
You may be eligible for this study if you are aged 18 of older and are on the waitlist for autologous stem cell transplant.

Study details
Participants will be randomised by chance (like flipping a coin) into two groups. One group will receive a physiotherapy assessment and standardised exercise advice in addition to standard care. The other group will attend 2 x 60 minute exercise classes per week and receive fortnightly phone calls comprising nutrition education for up to 8 weeks before their transplant. As part of this study, participants will also have a fitness and nutrition assessment, answer questionnaires, provide blood samples and consent to medical records being accessed.

It is hoped this research will demonstrate that prehabilitation builds physical strength and fitness, and this will to prevent problems after stem cell transplant, leading to faster recovery from treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100822 0
Dr Amy Dennett
Address 100822 0
Eastern Health Allied Health Clinical Research Office,
Level 2, 5 Arnold St Box Hill
Victoria 3128
Country 100822 0
Australia
Phone 100822 0
+61 390952442
Fax 100822 0
Email 100822 0
amy.dennett@easternhealth.org.au
Contact person for public queries
Name 100823 0
Dr Amy Dennett
Address 100823 0
Eastern Health Allied Health Clinical Research Office,
Level 2, 5 Arnold St Box Hill
Victoria 3128
Country 100823 0
Australia
Phone 100823 0
+61 390952442
Fax 100823 0
Email 100823 0
amy.dennett@easternhealth.org.au
Contact person for scientific queries
Name 100824 0
Dr Amy Dennett
Address 100824 0
Eastern Health Allied Health Clinical Research Office,
Level 2, 5 Arnold St Box Hill
Victoria 3128
Country 100824 0
Australia
Phone 100824 0
+61 390952442
Fax 100824 0
Email 100824 0
amy.dennett@easternhealth.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Anyone who wishes to access it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Unrestricted access via supplementary file of publication
What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 7339 0
Study protocol
Citation [1] 7339 0
Link [1] 7339 0
Email [1] 7339 0
Other [1] 7339 0
Study protocol including statistical analysis plan and details of ethical approval will be available through publication of protocol
Attachment [1] 7339 0
Type [2] 7341 0
Ethical approval
Citation [2] 7341 0
Link [2] 7341 0
Email [2] 7341 0
Other [2] 7341 0
Ethical approval attached to trial registration
Summary results
No Results