None listed
Conditions
Brief summary
There are clinical trials that have examined the benefits of supervised exercise training in addition to “optimal medical care” in peripheral arterial disease (PAD). However, aggressive risk factor modification was not the focus, as it has been in other (non-PAD) cardiovascular studies. This randomised controlled trial will evaluate the impact of a systematic physician-led approach to aggressive risk factor modification in PAD. Hypothesis: A multifactorial intervention in patients with PAD, compared to standard practice, will lead to improved functional status (as assessed by maximum walking distance [MWD]), cardiovascular risk factor control, and quality of life (as measured by Peripheral Artery Questionnaire). This systematic physician-led program will increase adherence to guideline-based therapies. There will be beneficial effects on the atherosclerotic disease process (as measured by exploratory biomarkers of inflammation). TRIAL DESIGN This is an investigator initiated, local, multicentre, randomised controlled trial in South Australia. A total of 150 participants will be randomised into two groups. The intervention arm (group A) will undergo multifactorial intervention under a physician-led program of behaviour modification with stepwise introduction of pharmacologic therapy. This group will have follow-up over a 12-month study period. The follow-up frequency will be up to the discretion of the study physician. The standard therapy arm (group B) will have conventional treatment (e.g. follow-up with general practitioner and/or vascular surgeon) for the length of the 12-month study period. These patients will be offered multifactorial intervention after completion of the protocol. The clinic reviews and investigations in this study are intended to complement standard practice. All participants will continue to see their usual treating clinicians throughout the study period.
Interventions
The aim of this study is to investigate the effects of a multifactorial intervention compared with standard treatment in patients with peripheral arterial disease. Patients with peripheral arterial disease are also at risk of coronary artery disease and cerebrovascular disease. Studies have shown that patients with peripheral arterial disease have suboptimal control of many cardiovascular risk factors.
This study is a prospective, local multi-centre randomised controlled trial. A total of 150 p
The aim of this study is to investigate the effects of a multifactorial intervention compared with standard treatment in patients with peripheral arterial disease. Patients with peripheral arterial disease are also at risk of coronary artery disease and cerebrovascular disease. Studies have shown that patients with peripheral arterial disease have suboptimal control of many cardiovascular risk factors. This study is a prospective, local multi-centre randomised controlled trial. A total of 150 participants will be randomised in a 1:1 ratio to an intervention arm (group A) and a control arm (group B). The total followup is 12 months. Group A (Intervention arm) Group A will undergo a multifactorial intervention with comprehensive lifestyle and medical program designed to manage cardiovascular risk factors. Intervention in group A is intended to complement standard practice. Multifactorial intervention will occur in the medical clinic setting and can include: Frequent review in a medical clinic Review of blood pressure, cholesterol and diabetes with introduction of medications to treat these conditions Smoking cessation program Structured exercise program Weight loss program Obstructive sleep apnoea screening and treatment Procedure Specifics: Medical history and medication review Review by medical physician. Details include: symptoms, past medical history, social history, medication history, and drug allergies and intolerances. If any clinically significant adverse event occurs, in the judgement of the investigator, it will be reported on the adverse event form. It is intended that group A participants are seen mainly by a single medical physician during the study period, to provide continuity of care. Blood pressure management Blood pressure will be measured during clinic review or using a home-based automated monitor. Group A participants with home-based monitoring will record values in a journal. Hypertension will be treated with target resting BP less than 130/80 mmHg at least 80% of the time. Participants with hypertension will be monitored with echocardiography to assess for left ventricular hypertrophy progression/ regression. An echocardiogram will be performed at baseline and upon study completion. Lifestyle modification for treatment of hypertension will include dietary salt restriction and/or weight loss program. Pharmacotherapy will be initiated in a stepwise fashion with a preference for angiotensin-converting enzyme inhibitors or angiotensin 2 receptor antagonists as first line treatment of choice. Lipid Management Serum lipid testing will be performed throughout the study. All participants will be commenced on statin medication, where tolerated. Lipid targets include: LDL less than 1.8 mmol/L and Non-HDL cholesterol less than 2.6 mmol/L. Treatment of dyslipidaemia will include dietary guidance and escalation of statin therapy to maximum tolerated dose. Additional therapy such as ezetimibe or fibrates may be introduced, where targets are not being met. Weight Management Where a group A participant has a BMI greater than or equal to 27kg/m2, they will be offered a weight management program. The goal will be for a BMI less than 27kg/m2 or at least 10% weight loss. The weight management program will emulate methodology executed in a previous cardiovascular risk factor modification study. Participants will have a structured motivational and goal-directed program with physician-led counselling. Meal plans will consist of a calorie-restricted diet with foods high in protein and a low glycaemic index. In addition, participants will commence a structured exercise program as described below. These participants will be encouraged to maintain a lifestyle journal with documentation of a nutritional intake and physical activities during the week. Weight management will be a priority throughout the duration of the study. Investigators will provide regular feedback and advice to participants via clinic follow-up and/or email contact. Frequency of contact at discretion of the treating physician. Exercise Therapy Group A participants will be offered an optional structured exercise program that is developed in consultation with an exercise physiologist. This plan is personalised and will consider the motivation and physical limitations of the individual. The program will begin with directly-supervised exercise therapy, and then a structured home-based exercise program thereafter. For example: An initial supervised exercise program occurs in an outpatient facility. Subsequently, the participant is counselled and given instructions for home-based exercise therapy, such as walking, cycling and/or lower limb training. The participant is encouraged to exercise until moderate-maximum claudication, alternating with periods of rest. The goal is to gradually increase the duration and/or intensity of prescribed activities. The participant logs an activity diary and keeps in regular contact with the healthcare provider (via regular email, and clinic). Clinic review will occur every 6-8 weeks with the exercise physiologist. Glycaemic Control Diagnosis of diabetes may be made with a fasting blood glucose test and/or HbA1c. Management of glycaemia could involve lifestyle modification and/or pharmacotherapy. Participants will be instructed about symptoms and management of hypoglcaemia. To reach target HbA1c less than 7%, group A participants may be referred to a specialised diabetes clinic. Smoking Cessation Group A participants will be encouraged to stop smoking. Smoking abstinence may be achieved by counselling and/ or pharmacotherapy. Medications such as nicotine replacement therapy, bupropion and/or varenicline may be commenced. Sleep-Disordered Breathing Management Participants in the intervention arm (group A) will undergo Berlin Questionnaire and home sleep testing (Apnea Link) screening at baseline. The results of these investigations will be made available to their usual treating clinicians. Participants with suspected obstructive sleep apnoea will be referred for review by a dedicated sleep disorder unit. The diagnosis can be confirmed with an overnight polysomnography test. Group A participants with an elevated apnoea-hypopnoea index (at least 30/hour) will be offered continuous positive airway pressure (CPAP) therapy.
Sponsors
South Australian Health and Medical Research Institute (SAHMRI)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Established symptomatic peripheral arterial disease with diagnosis confirmed by either: - Ankle brachial index (ABI) less than or equal to 0.9 OR - Specialist review OR - Documented history of a previous lower limb revascularisation procedure 2. Aged between 18 and 80 at the time of enrolment
Exclusion criteria
1. Known to a physician specifically for optimisation of atherosclerotic risk factors 2. Acute coronary syndrome and/or invasive coronary intervention (such as coronary artery bypass graft surgery or percutaneous coronary intervention) within 12-months prior to screening. 3. Planned lower limb revascularisation procedure within 3 months of screening 4. Presence of congestive heart failure (CHF) 5. Transient ischaemic attack (TIA) or stroke within 12-months prior to screening. 6. Other clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, haematological or metabolic disease that is, in the opinion of the investigator, not stabilised or may otherwise confound the results of the study. 7. Other co-morbidities which would, in the investigator’s judgement, prevent the participant from successfully completing protocol requirements. These include (but are not limited to): unstable critical limb ischemia, lower limb ulceration and/or amputation(s), severe respiratory disease; neurological dementia; end-stage renal disease with estimated glomerular filtration rate (EGFR<30 mL/min) or undergoing haemodialysis; thrombocytopenia as defined by a platelet count <100 x 10^9; active malignancy; active autoimmune or systemic inflammatory disease; severe hepatic failure 8. Estimated life expectancy less than 24 months 9. Not willing to attend regular follow-up 10. Female participants cannot be pregnant or breastfeeding 11. Participants whom, in the investigator’s judgement, cannot provide adequate informed consent
Outcome results
None listed