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Trial registered on ANZCTR


Registration number
ACTRN12620000408987p
Ethics application status
Not yet submitted
Date submitted
20/02/2020
Date registered
26/03/2020
Date last updated
26/03/2020
Date data sharing statement initially provided
26/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Structured exercise prograM to reduce Fatigue In patients receiving dialysis: a preference-stratified adaptive Trial (M-FIT)
Scientific title
Structured exercise prograM to reduce Fatigue In patients receiving dialysis: a preference-stratified adaptive Trial (M-FIT)
Secondary ID [1] 297651 0
None
Universal Trial Number (UTN)
Trial acronym
M-FIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
End stage kidney disease 313143 0
dialysis 313144 0
Condition category
Condition code
Renal and Urogenital 311618 311618 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a home exercise app for mobile phones, with monthly exercise physiologist check up sessions (one-on-one, held at the exercise clinic at each site)
a) The app will have exercise videos and a small paragraph of written instructions so that patients can follow along. Exercise physiologists will demonstrate how to navigate the app, input their scores for patient-reported outcomes (fatigue, quality of life, exercise adherence etc.) There will be no hard copy/physical information given out.
b) The app will have three streams of exercise (by type), into one of which participants will be randomised (please see the statistical analysis section for more details): 1) resistance (3 non-consecutive days/wk (~60 mins per session); 8-10 exercises of major muscle groups, Load/weight 60-70% reps max e.g. warm up stretches, sit to stand, wall push-up, standing leg curl ~ 60 min/session - exercises will differ each week), 2) cardio + resistance (3 non-consecutive days/wk (~60 mins per session); Aerobic RPE 11-13; Resistance Load/weight: 60-70% reps max e.g. warm up stretches, marches, wall push-up, air boxing) and 3) walking (3 non-consecutive days/wk (up to 180 mins total; warm up stretches)
c) exercise physiologist sessions will be face-to-face, exercise videos delivered through a mobile app
d) The duration of the intervention period is 3 months.
e) Patients will be followed up by an exercise physiologist face to face, once a month where difficulties/reasons for non adherence can be discussed. The first session will be an hour, followed by two 30-min sessions in the second and third months. Research team will monitor the completion of questionnaires on the app, including the self-report exercise adherence questionnaire.
Intervention code [1] 314673 0
Lifestyle
Comparator / control treatment
The control group will be given the mobile app as well to report the same patient-reported outcomes for 3 months (fatigue, quality of life etc.). They will be doing 3 non-consecutive days of warm up stretches for about 5-10 mins at home, via the app (same as the treatment groups but without the exercises). Patients will only see the type of exercise that they have been assigned on the app (e.g. the control group will not have access to any exercise except the warm up stretches, and the resistance group will not have access to videos given to walking and cardio + resistance groups)
Control group
Active

Outcomes
Primary outcome [1] 320316 0
Fatigue as measured by Functional Assessment Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, at 3 months.
Timepoint [1] 320316 0
3 months after initiation of the intervention
Secondary outcome [1] 371226 0
Mortality
Timepoint [1] 371226 0
3 months after initiation of the intervention
Secondary outcome [2] 380561 0
cardiovascular disease (measured by MI, sudden cardiac death; data from patient medical records)
Timepoint [2] 380561 0
3 months
Secondary outcome [3] 380562 0
fatigue (measured by patient-reported outcome measures: Pittsburg Fatigability Scale, SONG-HD Fatigue)
Timepoint [3] 380562 0
monthly for 3 months
Secondary outcome [4] 380563 0
vascular access function (for HD patients only; measured by rate of intervention obtained from patient medical records)
Timepoint [4] 380563 0
3 months
Secondary outcome [5] 380564 0
technique survival (for PD patients only; measured by PD transfer to HD obtained from patient medical records)
Timepoint [5] 380564 0
3 months
Secondary outcome [6] 380565 0
adherence to exercise (measured study-specific, self-report questionnaire)
Timepoint [6] 380565 0
3 months
Secondary outcome [7] 380566 0
hospitalisation (measured by the number of hospitalisations via hospital admission data)
Timepoint [7] 380566 0
6 moths, 12 months
Secondary outcome [8] 380567 0
utility-based quality of life (measured by EQ-5D)
Timepoint [8] 380567 0
3 months
Secondary outcome [9] 380568 0
healthcare resource use (assessed by using data linkage (MBS, PBS, Hospital admissions))
Timepoint [9] 380568 0
3 months
Secondary outcome [10] 380569 0
Physical activity (Actigraph accelerometers for the duration of the intervention. We will use a matchbox-sized accelerometer (Actigraph GT3X+) worn on the wrist)
Timepoint [10] 380569 0
3 months
Secondary outcome [11] 380570 0
Fitness (chair stand test (lower body strength), arm curl test (upper body strength), chair sit and reach test (lower body flexibility), back scratch test (upper body flexibility), 8-foot up and go test (agility), 6 minute walk test (functional fitness) at the initial consultation and final follow up (3 months) with the exercise physiologist)
Timepoint [11] 380570 0
3 months
Secondary outcome [12] 380572 0
Frailty
Fried phenotype assessed at the sessions with exercise physiologist:
1. Shrinking: weight loss, unintentional, of greater than or equal to 4.5 kg in the past year/at follow-up (self-report and by direct measurement of weight)
2. Weakness: grip strength (dynamometer)
3. Poor endurance and energy: as indicated by self-report of exhaustion. Self-reported exhaustion, identified by two questions from the Center for Epidemiologic Studies Depression Scale (CES-D), is associated with stage of exercise reached in graded exercise testing, and is predictive of cardiovascular disease.
4. Slowness: Based on time to walk 4m, adjusting for standing height.
5. Low physical activity level: A weighted score of kilocalories expended per week was calculated based on each participant's report
Timepoint [12] 380572 0
3 months

Eligibility
Key inclusion criteria
Patients aged 18+ years who have received haemodialysis or peritoneal dialysis for at least 3 months, and English speaking will be eligible.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Already enrolled in a structured exercise program, unable to participate in any type of exercise (at the lowest level) or have a life expectancy of <12 months

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Initially, participants will state a preference for type of exercise (if
any), then will be randomised with equal probability to one of four arms (control, walking (A), resistance (B), cardio + resistance (C)), stratified by the participant stated preference. Using Bayesian
response adaptive randomisation, randomisation probabilities to each intervention will be updated as the trial progresses through scheduled interim analyses. The randomisation probability to each arm within each preference stratum will be updated such that it is proportional to the (posterior) probability that the arm is superior to all others, for members of that preference subgroup, with respect to the primary outcome. Superiority of an intervention within a preference subgroup will be declared if at any interim analysis, the probability of that intervention being superior to all others amongst participants in that preference subgroups exceeds the pre-specified threshold. Random assignment to any arm within a preference group will be suspended if after an interim analysis, the probability of that arm being the best for that subgroup is less than the pre-specified inferiority threshold. The
thresholds ware set at pre-specified values which have been determined via simulation to control the trial-wise probability of false positives (at <5%), while achieving maximal trial-wise power for each
hypothesis assuming an effect equal to the minimal important difference (MID).
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The trial is a Bayesian adaptive design. The probability of superiority of each arm over the others within each preference subgroup will be updated at pre-scheduled interim analyses after 100, 150, 200, 250, and 300 enrolments with final analysis at 400. At each interim we
will: 1) change the allocation probability to each arm according to the updated probabilities of superior efficacy; 2) stop enrolment to an arm due to futility when the probability of it being best falls < 5%; 3) stop accrual early for superiority if the probability of it being best is >95%.

Main analysis: Primary analysis will be on an intent-to-treat basis and performed within a Bayesian framework. We will address four hypotheses: H1: exercise decreases fatigue when compared to
structured non-exercise based activity (stretching); H2: there is a particular type of exercise that is most effective in reducing fatigue; H3: patient’s preference affects the benefit obtained by exercise;
H4: a particular type of exercise is more effective than the others among people with a given preference. These will be evaluated through linear models, where the change in fatigue from baseline
is the dependent variable, and interventions, stated preferences, and their interactions, the independent variables. Interactions will be used to test hypotheses H3 and H4. For all regression parameters we
will assume non-informative priors and inference based on the posterior probability of the hypothesis above. A posterior probability above 95% will constitute strong evidence to support each hypothesis.
Secondary and sensitivity analysis: The secondary outcomes will be evaluated with an analogous strategy, but a logistic and Poisson models will replace the linear model for binary and count
outcomes. For longitudinal measurements, we will use mixed models. We will analyse mediation of the intervention effect using the accelerometer data as a surrogate of exercise adherence. If baseline unbalance is observed, we will conduct sensitivity analysis by adding the respective covariates to the models. The impact of potential missing data will be studied and multiple imputation may be used
for covariates (no imputation will be done for outcomes).

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)
NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 302180 0
Government body
Name [1] 302180 0
NHMRC
Address [1] 302180 0
National Health and Medical Research Council
16 Marcus Clarke St, Canberra ACT 2601
Country [1] 302180 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Edward Ford Building, A27 Fisher Rd, University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 305096 0
None
Name [1] 305096 0
Address [1] 305096 0
Country [1] 305096 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 302862 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 302862 0
Hawkesbury Road, Westmead, Sydney, NSW 2145
Ethics committee country [1] 302862 0
Australia
Date submitted for ethics approval [1] 302862 0
26/04/2020
Approval date [1] 302862 0
Ethics approval number [1] 302862 0

Summary
Brief summary
The M-FIT study is a preference-stratified adaptive randomised trial addressing a patient-prioritised unmet need for a rare disease led by a multidisciplinary team of patients, clinicians, and researchers
with internationally recognised expertise in trials, dialysis, patient-reported outcomes, and exercise interventions. Our global Standardised Outcomes in Nephrology (SONG) initiative, involving over
2000 patients receiving dialysis, caregivers and health professionals from 100 countries, established fatigue as a critically important core outcome. Lifestyle (including exercise) interventions was
the top priority identified through our research priority setting partnership. Based on our systematic reviews, the evidence for exercise interventions remains very uncertain. We convened a patient
workshop to identify and prioritise exercise interventions for the M-FIT trial to ensure acceptability. M-FIT will generate high quality evidence of the efficacy and cost-effectiveness of a co-produced exercise program on fatigue and quality of life, hospitalisation, mortality and cost effectiveness
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91642 0
Prof Allison Tong
Address 91642 0
Centre for Kidney Research
176 Hawkesbury Road, Westmead NSW 2145
Country 91642 0
Australia
Phone 91642 0
+61 2 9845 1467
Fax 91642 0
Email 91642 0
allison.tong@sydney.edu.au
Contact person for public queries
Name 91643 0
Prof Allison Tong
Address 91643 0
Centre for Kidney Research
176 Hawkesbury Road, Westmead NSW 2145
Country 91643 0
Australia
Phone 91643 0
+61 2 9845 1467
Fax 91643 0
Email 91643 0
allison.tong@sydney.edu.au
Contact person for scientific queries
Name 91644 0
Prof Allison Tong
Address 91644 0
Centre for Kidney Research
176 Hawkesbury Road, Westmead NSW 2145
Country 91644 0
Australia
Phone 91644 0
+61 2 9845 1467
Fax 91644 0
Email 91644 0
allison.tong@sydney.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?
No other documents available
Summary results
No Results