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Trial registered on ANZCTR


Registration number
ACTRN12621001586808
Ethics application status
Approved
Date submitted
18/10/2021
Date registered
19/11/2021
Date last updated
7/11/2022
Date data sharing statement initially provided
19/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Cardiac Rehabilitation for transient ischaemic Attack and Mild-Stroke: the CRAMS randomised controlled trial.
Scientific title
Is an integrated traditional exercise-based cardiac rehabilitation program effective in improving functional exercise capacity for people with TIA or mild-stroke during the 6-months following commencement of the traditional cardiac rehabilitation program compared to usual care?
Secondary ID [1] 305577 0
None
Universal Trial Number (UTN)
Trial acronym
CRAMS trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
transient ischaemic attack 323992 0
stroke 323993 0
Condition category
Condition code
Cardiovascular 321496 321496 0 0
Other cardiovascular diseases
Stroke 321497 321497 0 0
Ischaemic
Physical Medicine / Rehabilitation 321498 321498 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cardiovascular Rehabilitation (CVR) program
The CVR program included in this study is typical of most contemporary phase II cardiac rehabilitation programs in Australia. The cardiac rehabilitation program is multidisciplinary, time-limited (once a week, 6-weeks), conducted in groups, health service-based, and has educational and supervised exercise components (one hour education plus one hour exercise). Members of the multidisciplinary team include exercise physiologists, physiotherapists, dietitians, psychologists, pharmacists and supervised university health students.

The main aim of the exercise sessions will be to increase cardiovascular fitness or exercise capacity by exercising large muscle groups. The best predictor of an increased risk of death from any cause in men with cardiovascular disease is exercise capacity. For every 1-MET increase in exercise, there is a 9% improvement in survival. The exercise sessions will be conducted in the same way as a typical cardiac rehabilitation program as many cardiac rehabilitation participants have co-morbidities, including stroke. All exercise sessions will be individually tailored for each of the participants and supervised by a physiotherapist and/or exercise physiologist. Participants will be encouraged to exercise at a moderate intensity as recommended in cardiac rehabilitation guidelines. This will be monitored and measured using the modified Borg Rate of Perceived Exertion (RPE) scale, encouraging participants to exercise at an RPE of 4-6. The 'talk test' will also be used to monitor intensity of exercise, encouraging participants to exercise at a level where they can talk in full sentences but they cannot sing. Examples of the types of exercises they will be completing in the exercise class are walking on a treadmill, cycling on a stationary bike, stepping up and down on a set of steps, where appropriate.

Members of the multi-disciplinary team will conduct group education sessions to increase the participant’s knowledge of their cardiovascular disease (CVD) condition and increase self-management skills for risk factor management. The education will be slightly modified compared to a typical cardiac rehabilitation program to include the anatomy and physiology of the brain, transient ischaemic attack (TIA) and ischemic stroke, and the management of stroke risk factors. The education sessions will cover: cardiac and brain anatomy and physiology; cardiac and stroke risk factors, modification and management of symptoms; how to deal with stress, anxiety and depression; cardiac and stroke medications; benefits of exercise and physical activity; and nutrition advice. The mode of delivery of these education sessions will be at the discretion of the health professional delivering each session. For example, they may involve multimedia presentations, informal group discussions and interactive activities.

A CVR program attendance list will be maintained to record participants adherence to the 6 session program, including both the exercise and education session, which will be run in succession over a 2-hour period one day a week.

People with heart disease will be recruited to this program to replicate a standard phase II cardiac rehabilitation program currently offered in Australia and to enable the integration of people with TIA, mild-stroke and heart disease in the same program. People with heart disease can be referred by cardiac rehabilitation health professionals, Cardiologists, General Practitioners or they can self-refer. All people with heart disease attending the program will complete initial and 6-week assessments and will take part in all exercise and education sessions. Although research outcomes will not be collected or analysed for this group as the evidence base for exercise-based cardiac rehabilitation for people with heart disease is well established.
Intervention code [1] 321973 0
Rehabilitation
Intervention code [2] 321974 0
Prevention
Intervention code [3] 321975 0
Lifestyle
Comparator / control treatment
Those randomised to the control group will participate in usual care following a TIA or mild-stroke. This typically consists of follow-up with a neurologist and little or no secondary prevention. Control participants will be wait-listed for the CVR program and will commence the CVR program 6-months after they have completed their baseline measures.
Control group
Active

Outcomes
Primary outcome [1] 329270 0
Functional exercise capacity (6-minute walk test). The 6-minute walk test (6MWT) is a commonly used objective measure of functional exercise capacity in cardiac rehabilitation and stroke. The distance an individual is able to walk along a flat 25–30 m walkway over a 6-min period, with breaks as required, is recorded. The test is a self-paced, submaximal test of exercise capacity, and has been found to have a moderate-to-high reliability and validity. A change in distance of 34 m is considered a clinically meaningful change in people post stroke.
Timepoint [1] 329270 0
Baseline (start of CVR program), 6-weeks (primary timepoint, end of CVR program) and 6-months (follow-up).
Secondary outcome [1] 401967 0
Physical activity levels. A triaxial commercial accelerometer (ActiGraph GT3X, Fort Walton Beach, FL) will be used to objectively assess physical activity. Participants will be asked to wear the monitor on their right hip during a typical week while awake for 7-consecutive days. The raw data collected by the accelerometer, counts, will be used to obtain the time spent in different physical activity intensities.
Timepoint [1] 401967 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [2] 401968 0
Body mass index. Height (m), weight (kg) and body mass index (kg/m2) will be recorded using a calibrated set of scales and a stadiometer.
Timepoint [2] 401968 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [3] 401970 0
Waist circumference. Waist circumference will be measured in centimetres using a stretch-resistant tape measure. The waist circumference will be recorded as the midpoint between the lower margin of the lowest palpable rib and the top of the iliac crest. The measure will be repeated twice.
Timepoint [3] 401970 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [4] 401972 0
Blood pressure. Blood pressure levels will be obtained using a sphygmomanometer (Welch-Allyn DS66) on the right arm of seated subjects. The measure will be repeated twice.
Timepoint [4] 401972 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [5] 401973 0
Health-related quality of life. Health-related quality of life will be assessed using the Assessment of Quality of Life (AQoL-6D). The AQoL-6D was developed in Australia and uses Australian importance weights. The AQoL-6D is self-administered and consists of 20-items covering: independent living, mental health, coping, relationships, pain and sense. A multi-attribute utility score is then obtained, where a score of 100 reflects best health. The AQoL-6D is reliable and valid in community settings and can be used in economic analyses.
Timepoint [5] 401973 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [6] 401974 0
Anxiety and depression. The Hospital Anxiety and Depression Scale (HADS) will be used for the assessment of anxiety and depression. This questionnaire is a 14-item self-reporting questionnaire comprised of 4-point Likert-scaled items covering the occurrence of symptoms of anxiety (HADS-A) and depression (HADS-D) over the past 2 weeks. Each item on the questionnaire is scored from 0–3, so that a person can score between 0 (best outcome) and 21 (worst outcome) for either anxiety or depression. The minimally clinically important difference for patients with CVD is 1.7.
Timepoint [6] 401974 0
Baseline (start of CVR program), 6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [7] 401975 0
Emergency department visits. Participants will be surveyed to determine if they have had any unplanned presentations to the emergency department during the study period. This information will then be verified, where possible, by hospital patient admission records accessed by the Stroke Liaison Nurses to ascertain the Australian Refined Diagnosis Related Group (AR-DRG) and Urgent Related Group (URG) classification code assigned to the admission.
Timepoint [7] 401975 0
6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [8] 402715 0
Hospital admissions. Participants will be surveyed to determine if they have had any unplanned hospital admissions during the study period. This information will then be verified, where possible, by hospital patient admission records accessed by the Stroke Liaison Nurses to ascertain the Australian Refined Diagnosis Related Group (AR-DRG) and Urgent Related Group (URG) classification code assigned to the admission.
Timepoint [8] 402715 0
6-weeks (end of CVR program) and 6-months (follow-up).
Secondary outcome [9] 402716 0
Direct intervention costs will be recorded prospectively. The intervention cost will include: (i) CVR multi-disciplinary team member’s time; (ii) buildings and space used; (iii) equipment used for the CVR program; (iv) transportation cost for participants; (v) recruitment costs.
Timepoint [9] 402716 0
6-weeks (end of CVR program).

Eligibility
Key inclusion criteria
Eligible participants must:
• be 18+ years old;
• have a documented transient ischaemic attack (TIA) or mild non-disabling ischaemic stroke within the previous 12 months (National Institutes of Health Stroke Scale (NIHSS) score 0-4);
• reside in the Australian Capital Territory.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they have:
• evidence of intracranial haemorrhage on a CT or MRI study
• undergone recent (<30 days) carotid endarterectomy
• evidence of disabling stroke as measured by modified Rankin Scale score of greater than or equal to 3
• New York Heart Association class II-IV symptoms of heart failure
• uncontrolled arrhythmias
• severe chronic obstructive pulmonary disease
• uncontrolled hypertension
• symptomatic peripheral artery disease
• unstable angina
• uncontrolled diabetes
• do not have adequate English language skills, including significant speech impairment, or cognitive skills to agree to take part om the study or participate in a group exercise program (may be guided by formal testing of cognition such as the MMSE)
• previously completed cardiac rehabilitation.

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)
Group allocation will be concealed using sealed, consecutively numbered opaque envelopes. Following each participant’s baseline assessment the next envelope in the sequence will be opened to reveal random allocation to one of two groups: the Cardiovascular Rehabilitation program or the 6-month wait-list control group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An investigator not involved in recruitment or assessments will use a computer generated random number sequence, with participants allocated in a 1:1 ratio.
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
Efficacy
Statistical methods / analysis
All participants who complete the baseline assessment and attend at least one CVR session will be included in the analysis. Descriptive statistics will be completed and feasibility measures will be reported as percentages. Data will be analysed according to group assignment for participants with TIA or mild-stroke following intention-to-treat principles. To analyse 6MWT-distance and all other secondary outcomes, methods for repeated measures analysis will be used. Linear (for continuous outcome data) and Generalised Linear (for Binary and Count outcome data) mixed-effects models for repeated measures will be used for between-within group comparisons and time-interactions analyses adjusting for demographic characteristics and other potential covariates, such as time since TIA or mild-stroke. All analyses will be conducted using either SPSS version 26 or STATA version 16. Any estimate will be reported with associated 95% confidence intervals. Significance level will be set at p<0.05.

The effect of the intervention on the rates of unplanned CVD-related hospital admissions and emergency department visits within the 6-months study period using a cost-effectiveness analysis will also be evaluated. Information on secondary measures such as health behaviour change (moderate-to-vigorous physical activity), BMI, waist circumference, quality of life (AQoL-6D), clinical and demographic information and the costs associated with the use and delivery of the CVR program will be used. A cost-utility analysis will be undertaken with a societal perspective using gained quality-adjusted life years (QALYs) as the measure of health effects. The impact on Health-Related Quality of Life (HRQOL) can be measured using the AQoL-6D and the incremental cost-effectiveness ratios (ICERs) per QALYs will be calculated. Information on the participants’ health service utilisation costs, based on the AR-DRG and URG classification codes will also be used. From these analyses, the additional cost per unit of health benefit gained over the lifetime (by using the CVR program compared to usual care) can be determined.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/04/2022
Actual
8/04/2022
Date of last participant enrolment
Anticipated
29/09/2023
Actual
Date of last data collection
Anticipated
29/03/2024
Actual
Sample size
Target
140
Accrual to date
46
Final
Recruitment in Australia
Recruitment state(s)
ACT
Recruitment hospital [1] 20779 0
The Canberra Hospital - Garran
Recruitment hospital [2] 20780 0
Calvary Public Hospital ACT - Bruce
Recruitment postcode(s) [1] 35593 0
2605 - Garran
Recruitment postcode(s) [2] 35594 0
2617 - Bruce

Funding & Sponsors
Funding source category [1] 309938 0
Government body
Name [1] 309938 0
ACT Health (Research & Innovation Fund)
Country [1] 309938 0
Australia
Primary sponsor type
Individual
Name
A/Prof Nicole Freene
Address
University of Canberra, University Drive, Bruce, ACT, 2617
Country
Australia
Secondary sponsor category [1] 310979 0
Individual
Name [1] 310979 0
Prof Rachel Davey
Address [1] 310979 0
University of Canberra, University Drive, Bruce, ACT, 2617
Country [1] 310979 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309657 0
University of Canberra Human Research Ethics Committee
Ethics committee address [1] 309657 0
Ethics committee country [1] 309657 0
Australia
Date submitted for ethics approval [1] 309657 0
05/10/2021
Approval date [1] 309657 0
04/11/2021
Ethics approval number [1] 309657 0
9351

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

Contacts
Principal investigator
Name 114930 0
A/Prof Nicole Freene
Address 114930 0
University of Canberra, University Drive, Bruce, ACT, 2617
Country 114930 0
Australia
Phone 114930 0
+61262015550
Fax 114930 0
Email 114930 0
nicole.freene@canberra.edu.au
Contact person for public queries
Name 114931 0
Nicole Freene
Address 114931 0
University of Canberra, University Drive, Bruce, ACT, 2617
Country 114931 0
Australia
Phone 114931 0
+61262015550
Fax 114931 0
Email 114931 0
nicole.freene@canberra.edu.au
Contact person for scientific queries
Name 114932 0
Nicole Freene
Address 114932 0
University of Canberra, University Drive, Bruce, ACT, 2617
Country 114932 0
Australia
Phone 114932 0
+61262015550
Fax 114932 0
Email 114932 0
nicole.freene@canberra.edu.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?
Functional exercise capacity (6-minute walk test), Physical activity levels, body mass index, waist circumference, blood pressure, Health-related quality of life, Anxiety and depression and socio-demographic variables (eg: age, gender).
When will data be available (start and end dates)?
2025 - 2030. This data will be available for 5 years.
Available to whom?
Researchers interested in a cardiac rehabilitation model for TIA and stroke.
Available for what types of analyses?
Statistical.
How or where can data be obtained?
De-identified data for this trial will be available upon request by emailing the principal investigator: Nicole.Freene@canberra.edu.au


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
EmbaseCardiovascular Rehabilitation for transient ischaemic Attack and Mild Stroke: the CRAMS effectiveness-implementation hybrid study protocol.2022https://dx.doi.org/10.1186/s12913-022-08797-3
N.B. These documents automatically identified may not have been verified by the study sponsor.