Trial of Nonsurgical Treatment of Intermittent Claudication Due to Femoro-popliteal Disease

July 11, 2019 updated by: Hull University Teaching Hospitals NHS Trust

Randomised Controlled Trial of Percutaneous Transluminal Angioplasty (PTA) Versus a Supervised Exercise Programme (SEP) in the Management of Intermittent Claudication (IC) Due to Femoro-popliteal Disease

Intermittent Claudication (IC)is a common condition characterised by pain in the muscles of the legs on exertion caused by "hardening of the arteries" and a reduced blood supply. The investigators know that the vast majority of people suffering from this condition remain stable and do not deteriorate, and thus in general the viability of legs is not at risk. The main aim of treatment, therefore, is to try and improve walking thus reducing the impact this problem has on patients life style. There are many methods of management of intermittent claudication, but the investigators do not know which produces the best results. This study aims to compare the short and medium term outcomes of exercise programmes, percutaneous transluminal angioplasty and a combination of the two treatments for patients with intermittent claudication.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intermittent claudication (IC) is a common problem in the UK's elderly population with a prevalence of 5 -10%. Intermittent claudication infers significant quality of life limitations, however, it is a disease which generally runs a benign course with >80% of patients remaining stable. Yet the annual mortality rate in claudicants approaches 5%, three times that of age and sex matched population, due to the high prevalence of co-morbidity. IC is under-recognised as a risk factor for coronary and cerebrovascular events. Sixty percent of claudicants die from coronary heart disease and 10% of them die from stroke. Treating the patient with claudication, therefore, is likely to pay high dividends in terms of reducing deaths from myocardial infarction and stroke. The most appropriate management of IC, therefore remains a topic for debate but potentially beneficial therapies include: supervised exercise programmes (SEP); & percutaneous transluminal angioplasty (PTA).

A recent Cochrane review of PTA versus non-surgical management for intermittent claudication highlighted only two appropriate studies. More recently the results of a randomized control trial from Sweden have been published. This emphasizes the dearth of reliable scientific data in this area. It is believed that aorta-iliac atherosclerosis is often a solitary disease as opposed to femoro-popliteal disease which is often a manifestation of more generalized atherosclerosis. Further, the 5-year PTA patency rates for aorta-iliac disease are much better than those for femoro-popliteal PTA. Therefore, PTA is a well-established treatment modality for aorta-iliac disease but its role in femoro-popliteal disease is debatable11. This trial aims to prove the most effective treatment modality for claudication due to femoro-popliteal disease.

The two treatment modalities in question work by different mechanisms. PTA increases the blood flow to the limb. Whereas, exercise works by a combination of factors including optimized structural and metabolic performance of skeletal muscle, improvement in rheological parameters, development of collaterals, improved walking technique and marked psychological benefit. Still the efficacy of any treatment modality in claudication is judged by improvements in the standard measures of lower limb ischaemia as suggested by the International Society of Cardiovascular Surgery (ISCVS). These are essentially segmental pressure measurements and walking distances.

The primary aim of any treatment for patients with peripheral vascular disease is to improve the quality of life (QoL) rather than prolong survival. Several studies have shown that the traditional measures of lower limb ischaemia bear little correlation to the patient's QoL and these therefore need to be assessed independently. Further, generic QoL measures on their own are not sensitive enough to detect minor changes in QoL and so disease-specific measures need to be included in the outcomes.

Evidence is accumulating that each episode of exercise to the onset of claudication pain followed by rest may be considered as a low-grade ischaemia-reperfusion injury (IRI). Repeated episodes of IRI may have a cumulative effect leading to vascular endothelial damage and progression of atherosclerosis. This may explain the excess cardiovascular mortality seen in these patients16. Most experimental work measuring the biochemical markers of IRI is done following an episode of acute exercise. Few studies have shown the effect of an exercise -training programme on the biochemical markers of IRI. We intend to investigate this as a secondary component to the trial.

Heat shock proteins (hsp) are ubiquitous proteins found in the cells of all organisms. They are mainly classified according to their molecular weight. In addition to being constitutively expressed heat shock proteins can be induced by a number of stressors including heat, ischaemia and oxidative stress. Members of the hsp70 family are the most extensively studied group of stress proteins and they have been implicated in the prevention of ischaemia-reperfusion induced apoptosis, necrosis and oxidative injury in a variety of cell types including the cardiac myocyte18. Studies have shown hsp and their antibodies in the serum of normal individuals. Anti-hsp70 antibody levels in serum have been shown to be higher in vascular patients (IC, critical ischaemia and aortic aneurysms). Heat shock proteins have been detected in atherosclerotic lesions in higher concentrations. It is postulated that hsp play a key role in the autoimmune pathogenesis of atherosclerosis. Levels of anti-hsp antibodies are elevated in patients with carotid and coronary atherosclerosis and this correlates with the degree of atherosclerosis. Measuring anti-hsp antibodies in patients with IC undergoing exercise over a period of time may provide further valuable evidence on the role of heat shock proteins in atherosclerosis.

The secondary outcome measures of cost effectiveness analysis will interest health planners and clinicians as the health service has limited resources and 'value for money' has become increasingly important.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • East Riding Of Yorkshire
      • Hull, East Riding Of Yorkshire, United Kingdom, HU3 2JZ
        • Academic Vascular Surgery Unit, Vascular Laboratory, Alderson House, Hull Royal Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Symptomatic unilateral Intermittent Claudication Femoro-popliteal lesion Angioplastiable lesion on duplex > 3 months on BMT

Exclusion Criteria:

  • Critical ischaemia Incapacitating systemic disease Inability to tolerate treadmill testing Ischaemic changes on ECG during treadmill testing Ipsilateral surgery / PTA in previous 6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PTA
Procedure: Percutaneous Transluminal Angioplasty (PTA)
PTA will be performed by a consultant interventional radiologist with no deviation from the standard protocol at Hull & East Yorshire Yospitals NHS Trust.
Active Comparator: SEP
Procedure: Supervised Exercise Programme (SEP)

SEP: Conducted 3 times per week for 12 weeks.The session will be supervised by a physiotherapist and conducted in the cardiac gym.

Each session begins with gentle warming up exercises followed by an exercise circuit of 6 stations(2 minutes each).

  1. Station 1-Step-ups(20-cm high step,alternating leg after 10 step-ups)
  2. Station 2-Exercise bicycles
  3. Station 3-Knee extensions with weights(2kg beanbag)
  4. Station 4-Heel raises
  5. Station 5-Knee bends(Alternating legs after 10 bends)
  6. Station 6-Rest station(2Kg Biceps curls) Gentle walk for 2minutes in between the stations to recover.For first 6weeks patients complete one full circuit, followed by on extra station/week, thus by 12weeks patients will complete 2 full circuits.Finally patients perform a series of gentle stretching and cooling down exercises.

This exercise programme was designed to comply with suggested guidelines based on a meta-analysis assessing the effectiveness of SEP for claudicants.
Active Comparator: PTA+SEP
Procedure: Combined Treatment
PTA will be performed according to routine protocol followed by enrollment of patient in SEP. SEP will commence in the week following PTA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Treadmill walking distances - Intermittent claudication distance(ICD),maximum walking distance(MWD)
Time Frame: Pretreatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pretreatment, 1, 3, 6, 12, 36, & 60 months post treatment
Ankle brachial pressure indices(ABPI) measured at rest and post exercise
Time Frame: Pretreatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pretreatment, 1, 3, 6, 12, 36, & 60 months post treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Patient Reported Walking Distances (PRWD)
Time Frame: Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Clinical outcomes(PTA patency,re-intervention rates, fatal&non-fatal events,amputation,mortality and ISCVS outcome)
Time Frame: Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Health economic analyses
Time Frame: Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Markers of ischaemia reperfusion
Time Frame: Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment
Heat-shock proteins
Time Frame: Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment.
Pre-treatment, 1, 3, 6, 12, 36, & 60 months post treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hull University Teaching Hospitals NHS Trust

Collaborators

University of Hull

Investigators

  • Principal Investigator: Peter T McCollum, FRCS, Academic Vascular Surgery Unit, University of Hull

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

November 25, 2008

First Submitted That Met QC Criteria

November 25, 2008

First Posted (Estimate)

November 26, 2008

Study Record Updates

Last Update Posted (Actual)

July 15, 2019

Last Update Submitted That Met QC Criteria

July 11, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HEY- REF-2424

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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