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Trial registered on ANZCTR


Registration number
ACTRN12621001475831
Ethics application status
Approved
Date submitted
14/09/2021
Date registered
28/10/2021
Date last updated
30/09/2022
Date data sharing statement initially provided
28/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Holistic Peripheral Artery Disease Management Trial (OPTIMAL)
Scientific title
A multicentre, parallel-group, randomised controlled trial to determine the effect of a holistic, multidisciplinary medical management program on control of key cardiovascular risk factors in people with peripheral artery disease
Secondary ID [1] 304311 0
None
Universal Trial Number (UTN)
Trial acronym
OPTIMAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral artery disease 322051 0
Condition category
Condition code
Cardiovascular 319776 319776 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention arm will receive the PAD-medical program for a period of six months. This is a telehealth-delivered program supporting people with PAD to manage relevant risk factors. Telehealth will involve videoconferencing between the study staff, located at James Cook University and the Townsville University Hospital, and participants in their own homes. Participants will use the Queensland Health 'pexip' application to videoconference with study staff, using their own smart devices if available, or using an iPad provided to them. The PAD-medical program includes the following components:
1) Support for regular home-based risk factor monitoring, including measuring blood pressure once daily and blood glucose three times daily. Blood pressure monitors and blood glucose monitors will be provided if participants do not already own a suitable monitor, and will receive instruction on correct monitoring technique and the recording of results during the induction visit. Participants will also receive reminders during the scheduled telehealth consultations with the study nurses and doctor to monitor their blood pressure and blood glucose.
2) Medication optimisation through videoconferencing. A study doctor/clinical nurse team will host audiovisual consultations with participants to review the results of their home-based risk factor monitoring, and other risk factors (glycated hemoglobin [HbA1c], smoking status, anti-platelet prescription status, and low density-lipoprotein-c [LDL-c]). Existing medications will be changed and new medications added if needed to optimise control of these risk factors according to current clinical guidelines (Asian Pacific Society of Atherosclerosis and Vascular Diseases, European Society of Cardiology, Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischaemia, and the American College of Cardiology & American Heart Association), to achieve the following targets: systolic blood pressure <140 mmHg, LDL-c <1.8 mMol, HbA1c <7%, smoking abstinence, and daily anti-platelet use. Medications will be focused on statins, ezetimibe, angiotensin converting enzyme inhibitors, thiazides, metformin, SGLT inhibitors, low dose aspirin and low dose rivaroxaban. The consultations will occur at baseline, 2 weeks, 4 weeks, 6 weeks, 12 weeks and 18 weeks. In addition to home-based blood pressure and blood glucose monitoring, HbA1c and LDL-c will be monitored by blood tests at baseline, six weeks, 12 weeks and 18 weeks. Additional risk factor monitoring (blood tests for HbA1c and LDL-c) will be ordered by the study doctor for each participant if deemed necessary (e.g. to monitor effectiveness of newly prescribed medications).
3) Exercise sessions through videoconferencing. An accredited exercise physiologist will conduct small, group-based exercise sessions with participants. This will occur twice weekly for the first 3 months, and once weekly for the second 3 months, whilst also encouraging participants to do the exercises at home outside of the scheduled sessions. The supervised exercise sessions will include up to six participants, and run for 60 minutes, 30-minutes of which will include actual exercises, involving a repeated sequence of 10 exercises over 5-minutes. The exercise sequence was designed to require minimal space, and no specialised equipment, and includes the following exercises: marching on the spot, calf and toe raises, knee lifts, butt kicks, side steps, toe backwards taps, heel forward taps, toe side taps, and squats. Each exercise has regression (easier) and progression (harder) versions which individual participants may choose to perform as needed based on fitness level and claudication pain. Exercise intensity is intended to be moderate, where intermittent claudication pain levels reach moderate severity (3 to 4 out of 5) as indicated in current guidelines (ESSA position statement on exercise prescription for patients with PAD, and the scientific statement from the American Heart Association). The exercise physiologist will also conduct pre- and post-exercise safety checks with each participant.
4) Smoking cessation counselling through videoconferencing. For participants that are active smokers and want to quit smoking, a trained counsellor will deliver at least five monthly 30-minute sessions to each participant. Participants can request up to an additional five monthly sessions if needed (maximum of two per month). The sessions will involve the provision and education of pharmacological quitting aids (from the RACGP support smoking cessation guidelines) in conjunction with the study doctor, and individualised counselling on quitting using the 5As framework.
Adherence to the components of the intervention described above will be monitored through a self-reported diary for recording blood pressure and blood glucose measurements, and participation logs for the consultation sessions made by the study nurses, doctor, accredited exercise physiologist, and smoking cessation counsellor.
Intervention code [1] 320674 0
Treatment: Drugs
Intervention code [2] 320675 0
Treatment: Other
Intervention code [3] 320676 0
Lifestyle
Comparator / control treatment
Standard care by participants' usual general practitioner and vascular surgeon, including education on peripheral artery disease and its risk factors, regular risk factor monitoring, medication prescribing according to clinical guidelines, and revascularisation if needed according to clinical guidelines.
Control group
Active

Outcomes
Primary outcome [1] 327799 0
A composite outcome: the PAD-medical score. This score assigns a score based on the relative control of modifiable risk factors: LDL-c, systolic blood pressure, HbA1c, anti-thrombotic therapy, smoking status, and daily physical activity. The minimum score is zero (worst control), and maximum score is six (optimal control of each risk factor). Data for calculation of the PAD-medical score will be collected during (blood pressure, anit-thrombotic therapy and smoking status) and after (HbA1c and LDL by ordered blood tests, and daily physical activity by a seven-day step count using an Actigraph watch) the baseline and 6-month visits.
Timepoint [1] 327799 0
Baseline visit and 6 month post-baseline visit.
Secondary outcome [1] 401640 0
Mean systolic and diastolic blood pressure; assessed using a blood pressure monitor during the two in-person assessments by outcome assessors.
Timepoint [1] 401640 0
Baseline and 6 months post-baseline visit.
Secondary outcome [2] 401641 0
Mean HbA1c %; assessed by blood tests ordered by the outcome assessors and received within 7 days of the two in-person assessments.
Timepoint [2] 401641 0
Baseline and 6 months post-baseline visit.
Secondary outcome [3] 401642 0
Mean LDL-c; assessed by blood tests ordered by the outcome assessors and received within 7 days of the two in-person assessments.
Timepoint [3] 401642 0
Baseline and 6 months post-baseline visit.
Secondary outcome [4] 401643 0
Smoking status; assessed by questionnaire and biochemically verified using a piCO smokerlyzer by the outcome assessors during the two in-person assessments.
Timepoint [4] 401643 0
Baseline and 6 months post-baseline visit.
Secondary outcome [5] 401644 0
Daily physical activity; the seven-day step count assessed through use of an Actigraph watch which is worn for a period of seven days commencing during the two in-person assessments.
Timepoint [5] 401644 0
Baseline and 6 months post-baseline visit.
Secondary outcome [6] 401645 0
Health-related quality of life (HRQOL), assessed through the generic SF-36, which has been validated for use in PAD. The questionnaire will be self-completed by participants during the two in-person assessments.
Timepoint [6] 401645 0
Baseline and 6 months post-baseline visit.
Secondary outcome [7] 401647 0
Health-related quality of life (HRQOL), assessed through the disease-specific Intermittent Claudication Questionnaire (ICQ) which we specifically designed and validated to assess HRQOL in people with intermittent claudication and chronic limb threatening ischemia. The questionnaire will be self-completed by participants during the two in-person assessments.
Timepoint [7] 401647 0
Baseline and 6 months post-baseline visit.
Secondary outcome [8] 401648 0
Health-related quality of life (HRQOL), assessed through the peripheral artery disease quality of life (PADQOL) questionnaire which we specifically designed and validated to assess HRQOL in people with intermittent claudication and chronic limb threatening ischemia. The questionnaire will be self-completed by participants during the two in-person assessments.
Timepoint [8] 401648 0
Baseline and 6 months post-baseline visit.
Secondary outcome [9] 401650 0
Walking ability, assessed through a six-minute walk test which has been validated for PAD, conducted during the two in-person assessments.
Timepoint [9] 401650 0
Baseline and 6 months post-baseline visit.
Secondary outcome [10] 401651 0
Patient-reported adherence to prescribed medications, and home blood pressure and blood glucose measurements, assessed by outcome assessors during the second of two in-person assessments, and by phone at the two year assessment.
Timepoint [10] 401651 0
6 months post-baseline visit, and 2 years post-baseline phone call.
Secondary outcome [11] 401652 0
Major adverse cardiovascular and limb events defined as a composite of myocardial infarction, stroke, requirement for revascularization and major amputation. Vascular surgical procedures will include endovascular and open coronary revascularization, lower limb peripheral revascularization (open or endovascular) and carotid artery revascularization. These will be assessed through questioning participants during the second of two in-person assessments, and by phone at the two year assessment. If participants have been lost to follow-up, data linkage to medical records will be used.
Timepoint [11] 401652 0
6 months post-baseline visit, and 2 years post-baseline phone call.
Secondary outcome [12] 401653 0
Patient engagement with the intervention, assessed through recording attendance at scheduled exercise sessions, completion of planned blood tests and blood pressure recordings, and attendance at scheduled telehealth physician consults over the six-month program.
Timepoint [12] 401653 0
Collected through trial and quantified after 6 months post-baseline visit.
Secondary outcome [13] 401654 0
Participant satisfaction with the intervention, assessed at six months using a questionnaire that has been specifically designed for this purpose, and a semi-structured interview for those who consent to participate in the interview.
Timepoint [13] 401654 0
6 months post-baseline visit.
Secondary outcome [14] 401655 0
Circulating biomarkers of PAD pathology in a subgroup of consenting participants and where it is feasible to obtain blood samples for a biomarker sub study. This is an exploratory outcome, for which participants can consent to have additional blood taken for the biomarker sub-study. This will be assessed by a blood sample taken in conjunction with samples for their HbA1c and LDL-c within 7 days of the two in-person assessments.
Timepoint [14] 401655 0
Baseline and 6 months post-baseline visit.
Secondary outcome [15] 401656 0
Hospital admissions for any cardiovascular cause including for any cardiovascular operation or treatment of any cardiovascular event or disease. These will be assessed through questioning participants during the second of two in-person assessments, and by phone at the two year assessment. If participants have been lost to follow-up, data linkage to medical records will be used.
Timepoint [15] 401656 0
6 months post-baseline visit, and 2 years post-baseline phone call.

Eligibility
Key inclusion criteria
1. PAD, defined from prior diagnosis by an appropriately qualified specialist including vascular surgeon, cardiologist or internal medicine specialist. PAD diagnosis will consider symptoms, clinical examination, past requirement for surgical treatment of PAD and available investigations including ankle brachial index (ABI), duplex ultrasound or angiography. Acceptable definitions will include ABI <0.9 or >1.4, absence of pedal pulses with relevant symptoms, prior requirement for lower limb peripheral artery open surgical or endovascular procedure to treat athero-thrombosis or imaging (including ultrasound, digital subtraction angiography, computed tomography or magnetic resonance imaging) evidence of lower limb artery stenosis (at least 50%) or occlusion;
2. At least 18 years old and able to provide valid informed consent;
3. Able to verbally communicate with the trial staff in English.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Enrolled in another clinical trial;
2. Optimal risk factor control (i.e. PAD-medical score 6);
3. Unwilling or unable to engage with technology required for intervention;
4. Terminal illness with a prognosis of less than 6 months.

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)
Allocation will be concealed through use of an off-site randomisation service.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random sequence for study arm allocation will be generated prior to commencement. Randomisation will be conducted using a secure, independent web-based minimisation randomisation system (Sealed Envelope), and will be stratified by study centre, gender and PAD-medical score (<3, 3 to 4 and >4). Randomisation will be in a 1:1 ratio between the PAD-medical group and the usual care group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All randomised participants will be included in the primary analysis, and will be analysed according to their randomly allocated treatment. Statistical analyses will be conducted according to a detailed pre-specified data analysis plan which will be published separately prior to completion of the trial. A brief account of the statistical methods is included here.
The hypothesis testing of continuous primary and other outcomes will be performed using unpaired t-test or Mann Whitney U tests (depending on data distribution) to compare groups. A p-value <0.05 will be considered significant. Qualitative data from the interviews and surveys will analysed using content analysis to identify and quantify key concepts in relation to the acceptability of PAD-medical. Transcribed interviews will undergo thematic analysis independently by two research team members, involving deductive coding based on the program objectives. NVivo qualitative data analysis software will be used to assist in the analysis. Assessments of congruence (data triangulation) between the quantitative and qualitative findings will be conducted, to identify points of convergence and divergence between the datasets. For major adverse cardiovascular events, time-to-event analysis will be conducted. The HR and 95% CI will be calculated using Cox proportional hazard analysis, and event risk will be plotted on a Kaplan-Meier graph. A p-value <0.05 will be considered significant. For major adverse cardiovascular events, time-to-event analysis will be conducted. The HR and 95% CI will be calculated using Cox proportional hazard analysis, and event risk will be plotted on a Kaplan-Meier graph. A p-value <0.05 will be considered significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2021
Actual
1/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
246
Accrual to date
40
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19663 0
Townsville University Hospital - Douglas
Recruitment hospital [2] 19664 0
Mater Hospital Pimlico - Pimlico
Recruitment hospital [3] 19665 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 19666 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 19667 0
Sunshine Coast University Hospital - Birtinya
Recruitment postcode(s) [1] 34296 0
4814 - Douglas
Recruitment postcode(s) [2] 34297 0
4810 - Pimlico
Recruitment postcode(s) [3] 34298 0
4029 - Herston
Recruitment postcode(s) [4] 34299 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 34300 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 308685 0
Charities/Societies/Foundations
Name [1] 308685 0
Heart Foundation
Country [1] 308685 0
Australia
Primary sponsor type
University
Name
James Cook University
Address
1 James Cook Drive, Townsville, QLD, 4811
Country
Australia
Secondary sponsor category [1] 309837 0
None
Name [1] 309837 0
Address [1] 309837 0
Country [1] 309837 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308607 0
Townsville Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 308607 0
Ethics committee country [1] 308607 0
Australia
Date submitted for ethics approval [1] 308607 0
21/06/2021
Approval date [1] 308607 0
12/08/2021
Ethics approval number [1] 308607 0

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

Contacts
Principal investigator
Name 111310 0
Prof Jonathan Golledge
Address 111310 0
JCU Research Block, Ground Floor
Townsville University Hospital
100 Angus Smith Drive, Douglas, QLD, 4814
Country 111310 0
Australia
Phone 111310 0
+61 7 4781 4838
Fax 111310 0
Email 111310 0
[email protected]
Contact person for public queries
Name 111311 0
Aaron Drovandi
Address 111311 0
JCU Research Block, Ground Floor
Townsville University Hospital
100 Angus Smith Drive, Douglas, QLD, 4814
Country 111311 0
Australia
Phone 111311 0
+61 7 4781 3437
Fax 111311 0
Email 111311 0
[email protected]
Contact person for scientific queries
Name 111312 0
Jonathan Golledge
Address 111312 0
JCU Research Block, Ground Floor
Townsville University Hospital
100 Angus Smith Drive, Douglas, QLD, 4814
Country 111312 0
Australia
Phone 111312 0
+61 7 4781 4838
Fax 111312 0
Email 111312 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
No additional documents have been identified.