Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000744853
Ethics application status
Approved
Date submitted
14/04/2021
Date registered
11/06/2021
Date last updated
11/06/2021
Date data sharing statement initially provided
11/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Lower limb rehabilitation for patients with peripheral artery disease.
Scientific title
Feasibility of using the cardiac rehabilitation model in patients with peripheral artery disease: the PAD-CRM study.
Secondary ID [1] 302312 0
None
Universal Trial Number (UTN)
U1111-1258-2959
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral Artery Disease 319072 0
Condition category
Condition code
Cardiovascular 317024 317024 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will start their individualised exercise program by walking on a treadmill at a natural gait speed chosen by the patient. Walking intensity will be monitored using a claudication rating scale (i.e. where 0=no pain; 1=onset of pain; 2=mild; 3=mild-to-moderate; 4=moderate; 5=maximum), and exercise that induces claudication pain of a moderate severity (i.e. 3 to 4 out of 5) will be prescribed. When this target is achieved, the participant will be asked to stop walking and will be instructed to continue exercising using an alternative method of resistance training (either leg press, calf press, chest press or seated row) or aerobic exercise (arm ergometer, stationary bike). Moderate exercise intensity will be targeted for the alternative exercises, commencing at a rating of perceived exertion (RPE) of 13-15 on a 20-point BORG scale. For resistance training, a moderate exercise intensity of 60% of 1 repetition maximum (1RM) will be prescribed and participants will undertake 3 sets of 8 repetitions. After sufficient time to recover from claudication pain, participants will return to the treadmill and resume walking again until they reach a level of exercise that induces moderate claudication pain, and then again switch to an alternative method of resistance or aerobic exercise. Participants will continue to alternate between walking at a moderate level and alternative exercises until 30 minutes of aerobic exercise has been completed and all 4 of the resistance training exercise have been completed. The participants heart rate and blood pressure will be monitored throughout exercise, to assess for an exaggerated response to exercise that may lead to early cessation, as well as to help determine the appropriate intensity of exercise using the 20-point BORG scale. This exercise will be prescribed by an accredited exercise physiologist and investigator (B. Parmenter) and the type and intensity of exercises will be documented in the participants records. Each participant will attend 2 x supervised exercise training sessions per week, lasting for 1-2 hours in duration, and attendance at these visits will be documented in the participants records. The cardiac rehabilitation centres at each participating site have fully equipped gyms, and they will be used for delivering supervised exercise programs. This exercise program follows current best-practice guidelines, recommended by the Exercise and Sports Science Australia (ESSA), as outlined in the a position statement on exercise prescription for patients with peripheral artery disease and intermittent claudication: Askew C.D., Parmenter B et.al., Journal of Science and Medicine in Sport; 2014:17:623-9. In addition, the supervised exercise program will incorporate other strategies designed for medical optimisation, including a review of the participants comorbidities, risk factors for atherosclerotic cardiovascular disease, and the appropriate use of optimal guideline-directed medical therapy to achieve recommended therapeutic targets for traditional risk factors (including total cholesterol, LDL-cholesterol, blood pressure, and HbA1c). Medication compliance will be assessed and documented in the participants records. Counselling will be provided on the importance of medication use, the health benefits of medication use and compliance, common side effects and when to be worried. Behavioural modification will also be offered in the form of counselling on healthy lifestyle choices, including the importance of a healthy diet and compliance with exercise, achieving weight loss, and smoking cessation, if appropriate. Personal health goals will be set with the participant using shared decision making and advice will be given on self-management regarding positive lifestyle changes, including identifying current tobacco smoking and providing recommendations for successful cessation, referrals to the Quit Line and the Get Healthy Service. Support for this level of self-management will also be offered as per usual cardiac rehab programs, targeting motivational and behavioural change strategies to help participants to comply with exercise goals, and a healthy lifestyle. A HADS depression score will be used to assess for depression at baseline and form a basis to guide further counselling and/or therapy specifically targeting mental health. These aspects of the supervised rehabilitation program will be delivered by study nurses at each site (Nursing Unit Manager’s: Alexander Slattery at Liverpool Hospital and Wendy Mullooly at Sutherland Hospital), and study cardiologist, with second weekly review by the study cardiologist to maximise medical therapy. Following the 8-week program, participants will be given a long-term, evidence-based home exercise program, written by exercise physiologist and advised to follow up with their GP.
Intervention code [1] 318602 0
Rehabilitation
Comparator / control treatment
This is a single arm pilot trial, as such there is no comparator
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325129 0
The primary outcome will be feasibility of the lower limb rehabilitation program, which will be measured as the percentage of PAD patients referred who attend and complete the program as compared with the reference standard for cardiac rehabilitation. A positive result will be defined as >=80% of eligible PAD patients approached accepting a referral and >=65% completing the 8-week program with an attendance (adherence) rate of >=80%. This will be performed by conducting an audit of the participants records, obtained during the supervised exercise sessions.
Timepoint [1] 325129 0
At the conclusion of the study.
Secondary outcome [1] 386947 0
Body Mass Index (BMI):
Height will be measured in metres (m) using a stadiometer and weight will be measured in kilograms (kg) using calibrated digital scales, according to anthropometric guidelines. BMI will be calculated from these readings (using the following formula: weight (kg) divided by height (m) squared).
Timepoint [1] 386947 0
BMI will be assessed at 3 time points: baseline, 8 weeks and at 6 months.
Secondary outcome [2] 393586 0
Resting peripheral blood pressure (BP) will be measured in the arm using a validated, automated sphygmomanometer and recorded in millimeters of mercury (mmHg) after 10 minutes of rest.
Timepoint [2] 393586 0
Baseline, 8 weeks and 6 months.
Secondary outcome [3] 393591 0
Tobacco smoking status will be assessed as a part of a clinical history and will be obtained by self-report. Smoking status will be recorded as "active" or "past" (including the number of days or weeks of cessation), or "never".
Timepoint [3] 393591 0
Baseline. 8 weeks and 6 months.
Secondary outcome [4] 393592 0
Claudication distance, defined as the distance in metres (m) walked until the onset of lower limb claudication pain, will be assessed during a 6-minute walk test performed on a flat surface. Participants will be asked to walk as fast and for as long as they can within 6 minutes and to report when they experience the initial onset of claudication pain.
Timepoint [4] 393592 0
Baseline, 8 weeks and 6 months.
Secondary outcome [5] 393595 0
Muscle strength, defined as the maximum weight measured in kilograms (kg) lifted during a single repetition when conducting a resistance or weight-bearing exercise (e.g. leg press, chest press, calf press or seated row). The participant will be asked to lift a steadily increasing weight, as a single repetition at 1 minute intervals when above a BORG RPE > 15 (out of 20), until the patient cannot complete a complete range of motion for this given weight, while maintaining correct posture and technique, after 2 attempts. The last weight (in kg) successfully lifted with a full range of motion and correct technique will be recorded as the participants muscle strength. This will be assessed for each of the 4 resistance exercises (leg press, chest press, calf press or seated row), and as a composite score (the sum divided by 4).
Timepoint [5] 393595 0
Baseline, 8 weeks and 6 months.
Secondary outcome [6] 393596 0
Health-related quality of life score will be assessed using the EQ-5D-5L score, calculated on scores obtained from an assessment of the following domains: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. In addition, an overall perception of quality of life is obtained, and scored out of 100 (i.e. 0=worst imaginable health status, and 100=best imaginable health status). The 5-level EQ-5D version (EQ-5D-5L) was introduced by the EuroQol Group in 2009 to improve the instrument’s sensitivity and to reduce ceiling effects, as compared to the EQ-5D-3L. The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/
Timepoint [6] 393596 0
Baseline, 8 weeks and 6 months.
Secondary outcome [7] 393597 0
Medication compliance will be assessed by reviewing the prescribed medications and documenting the use of these medications, as obtained by self-report. This will be documented in the participants records.
Timepoint [7] 393597 0
Baseline, 8 weeks and 6 months.
Secondary outcome [8] 396403 0
6 minute walk distance, defined as the total distance in metres (m) walked within a timed period of 6 minutes, will be assessed using a 6-minute walk test performed on a flat surface. Participants will be asked to walk as fast and for as long as they can within 6 minutes.
Timepoint [8] 396403 0
Baseline, 8 weeks and 6 months.
Secondary outcome [9] 396404 0
Resting heart rate will be measured using a validated, automated sphygmomanometer and recorded as beats per minute after 10 minutes of rest.
Timepoint [9] 396404 0
Baseline, 8 weeks and 6 months.
Secondary outcome [10] 396405 0
Fasting blood glucose will be measured from samples obtained from venous sampling after an 8 hour fast. This parameter will be tested by standard enzymatic methods within accredited laboratories, according to National standards.
Timepoint [10] 396405 0
Baseline, 8 weeks and 6 months.
Secondary outcome [11] 396406 0
Exercise intensity, defined as a the average BORG RPE score achieved on each piece of exercise equipment used during supervised exercise training (on 20-point BORG scale), will be recorded. This is a composite score calculated as an average, and is derived from the individual BORG RPE scores achieved for each aerobic and resistance or weight-bearing exercise attempted during exercise sessions.
Timepoint [11] 396406 0
Baseline and 8 weeks.
Secondary outcome [12] 396407 0
Depression score will be assessed using the Hospital Anxiety and Depression Scale (HADS). This specifically addresses how the participate has been feeling in the past 1 week. A cumulative score is calculated from each domain (with a maximum value of 21), which provides an assessment as follows: "normal"=0-7, "borderline abnormal"=8-10, and "abnormal"=11-21.
Timepoint [12] 396407 0
Baseline, 8 weeks and 6 months.
Secondary outcome [13] 396408 0
A participant satisfaction survey, designed to gauge the level of consumer satisfaction in participating in the cardiac rehabilitation model for patients with peripheral artery disease, will be delivered. This survey is study-specific and is not a validated research tool. It is designed to obtain information from participants on their experiences and opinions to inform future research.
Timepoint [13] 396408 0
Baseline, 8 weeks and 6 months.
Secondary outcome [14] 396431 0
Total cholesterol will be measured from samples obtained from venous sampling after an 8 hour fast. This parameter will be tested by standard enzymatic methods within accredited laboratories, according to National standards.
Timepoint [14] 396431 0
Baseline, 8 weeks and 6 months.
Secondary outcome [15] 396432 0
Low density lipo-proteins will be measured from samples obtained from venous sampling after an 8 hour fast. This parameter will be tested by standard enzymatic methods within accredited laboratories, according to National standards
Timepoint [15] 396432 0
Baseline, 8 weeks and 6 months.
Secondary outcome [16] 396433 0
High density lipo-proteins will be measured from samples obtained from venous sampling after an 8 hour fast. This parameter will be tested by standard enzymatic methods within accredited laboratories, according to National standards.
Timepoint [16] 396433 0
Baseline, 8 weeks and 6 months.
Secondary outcome [17] 396434 0
Triglycerides will be measured from samples obtained from venous sampling after an 8 hour fast. This parameter will be tested by standard enzymatic methods within accredited laboratories, according to National standards.
Timepoint [17] 396434 0
Baseline, 8 weeks and 6 months.

Eligibility
Key inclusion criteria
1) aged >=18 years.
2) a diagnosis of lower limb PAD established by a medical practitioner.
3) clinically stable PAD (i.e. stable intermittent claudication for at least 3 months not requiring revascularisation).
4) ability to walk.
5) community-dwelling (i.e. not residing in a nursing home or hostel).
6) able to consent to participate in the study.
7) competent in English at a level sufficient for study participation unless a translator is available.
8) able to participate in the study and comply with the study requirements over 6 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) persons who are already enrolled in another study and/or;
2) an absolute or relative contraindication to participate in, or successfully complete, an exercise-based rehabilitation program, including:
i) women who are pregnant
ii) participants with lower limb pain at rest due to PAD
iii) those with tissue loss or gangrene due to PAD
iv) unstable heart disease
v) severe heart failure or other severe heart condition
vi) unstable aneurysm or ballooning of artery as diagnosed by a medical specialist
vii) rapidly progressive or terminal illness
viii) severe memory problems due to dementia
ix) severe psychosis or psychological illness
x) current active substance (drug or alcohol) abuse

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size is 40 participants was selected for this single arm feasibility study. There is no available data to support a sample size calculation, however, the investigators expect that n=40 will be sufficient to calculate variance estimates to derive a sample size for an adequately powered subsequent trial. Data arising from this study will be assessed for normality and where possible reported as mean and standard deviation, or median and interquartile range as appropriate, and analysed using a repeated measures analysis of variance that incorporates baseline, 8-week and 6-month measures to maximize the efficiency of the analysis.
Analyses will be performed on descriptive data for the primary outcome and will be expressed as numbers and percentages. Comparisons between baseline and follow-up for secondary outcomes will be undertaken using chi-squared tests for categorical data, independent sample t-tests for normally distributed continuous data and Mann-Whitney U test for non-normally distributed continuous data. Statistical significance will be set at p<0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/06/2021
Actual
Date of last participant enrolment
Anticipated
12/10/2021
Actual
Date of last data collection
Anticipated
12/04/2022
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18992 0
The Sutherland Hospital - Caringbah
Recruitment hospital [2] 18993 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 33531 0
2229 - Caringbah
Recruitment postcode(s) [2] 33532 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 306736 0
University
Name [1] 306736 0
The University of New South Wales
Country [1] 306736 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The George Institute for Global Health
Address
Level 5, 1 King Street, Newtown, NSW 2042
Country
Australia
Secondary sponsor category [1] 308945 0
University
Name [1] 308945 0
The University of New South Wales
Address [1] 308945 0
School of Health Sciences, Faculty of Medicine. UNSW Sydney NSW 2052.
Country [1] 308945 0
Australia
Other collaborator category [1] 281695 0
Hospital
Name [1] 281695 0
The Sutherland Hospital - Caringbah
Address [1] 281695 0
Department of Cardiology, The Sutherland Hospital, Kareena Rd, Caringbah NSW 2229
Country [1] 281695 0
Australia
Other collaborator category [2] 281696 0
Hospital
Name [2] 281696 0
Liverpool Hospital - Liverpool
Address [2] 281696 0
Department of Cardiology, Liverpool Hospital, Elizabeth &, Goulburn St, Liverpool NSW 2170
Country [2] 281696 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308227 0
University of New South Wales Human Research Ethics Committee
Ethics committee address [1] 308227 0
Ethics committee country [1] 308227 0
Australia
Date submitted for ethics approval [1] 308227 0
19/02/2020
Approval date [1] 308227 0
24/04/2020
Ethics approval number [1] 308227 0
HC200146
Ethics committee name [2] 308229 0
South Eastern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [2] 308229 0
Ethics committee country [2] 308229 0
Australia
Date submitted for ethics approval [2] 308229 0
15/09/2020
Approval date [2] 308229 0
09/11/2020
Ethics approval number [2] 308229 0
2020/ETH01346

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

Contacts
Principal investigator
Name 105406 0
Dr Clare Arnott
Address 105406 0
The George Institute for Global Health
Level 5, 1 King St, Newtown NSW 2042.
Country 105406 0
Australia
Phone 105406 0
+61 2 8052 4823
Fax 105406 0
Email 105406 0
[email protected]
Contact person for public queries
Name 105407 0
Clare Arnott
Address 105407 0
The George Institute for Global Health
Level 5, 1 King St, Newtown NSW 2042.
Country 105407 0
Australia
Phone 105407 0
+61 2 8052 4823
Fax 105407 0
Email 105407 0
[email protected]
Contact person for scientific queries
Name 105408 0
Belinder Parmenter
Address 105408 0
Department of Exercise Physiology, Faculty of Medicine and Health
Room 254, Level 2 West, Wallace Wurth Building, UNSW
Randwick NSW 2031
Country 105408 0
Australia
Phone 105408 0
+61 2 9065 7411
Fax 105408 0
Email 105408 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data will be available for sharing, including clinical characteristics (age, sex, comorbidities), cardiovascular risk factors (fasting lipids, SBP and DBP, fasting BSL, BMI and tobacco smoking status), functional assessment, quality of life and depression scores, and medication compliance.
When will data be available (start and end dates)?
Data will be available at the completion of the study, which includes follow-up after a home-based exercise program at 6 months. Data will be available for 5 years after the publication date.
Available to whom?
Data will potentially be made available to researchers after submitting a valid research question and methodology, on a case-by-case basis, at the discretion of the primary sponsor.
Available for what types of analyses?
Data will be available for additional subgroup analyses and/or meta-analyses.
How or where can data be obtained?
Data will be available electronically and distributed by secure methods via the study investigators: Dr Clare Arnott ([email protected]) and Dr Belinder Parmenter ([email protected]).


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
No additional documents have been identified.