Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease (APOSA-PAD)
Peripheral arterial disease (PAD) is a common condition that arises due to the build up of atheroma in the arteries supplying blood to the peripheral muscles and other tissues. This imbalance between oxygen supply and demand becomes particularly apparent when patients with the condition are walking. The pain and weakness they experience (mainly in the calf but less commonly in the thigh) is known as intermittent claudication and resolves upon cessation of exercise.
It is an important disease to study as it is (i) common (est. prevalence of symptomatic intermittent claudication in Scotland of 4.5%) and (ii) those with it have a 1.6 times higher relative risk of ischaemic heart disease. These patients also have a significantly higher mortality than age-matched controls at around 12% per year.
There are two main aims of therapy - (i) to reduce the risk of cardiovascular events by way of standard secondary prevention measures (smoking cessation, anti-platelet, anti-hypertensive and cholesterol-lowering therapy, diabetic control) and (ii) to treat symptoms.
Supervised exercise therapy has been shown to be beneficial in improving walking time and distance in selected patients with leg pain from intermittent claudication with an overall increase in walking distance of approximately 150 metres at three months.
There are numerous drug treatments available for consideration in PAD patients (mainly cilostazol in the UK), but many of these have either undesirable side effects or no clear evidence of benefit. The range of increase in walking distance on cilostazol was reported to be a 50-76% increase over three months compared to 20% with placebo with some significant improvements in Quality of Life (QOL) indicators, although with a significant number of adverse effects (16% vs 8% on placebo) limiting therapy. The current cost (March 2010) is £35.31/month.
Other options for therapy include angioplasty and bypass surgery. At present these are only recommended for patients who fail to respond to medical therapy and have severely disabling symptoms (in the absence of significant exercise-limiting comorbidities).
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease|
- Onset of claudication pain [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]Our primary endpoint will be the distance to onset of claudication pain at 24 weeks but we will also measure total exercise distance.
- Quality of life [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]To see if allopurinol improves quality of life in patients with PAD.
- Anti-oxidant effects [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]To investigate the anti-oxidant effects of allopurinol of patients with PAD.
|Study Start Date:||February 2011|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Allopurinol
Participants will be given blinded medication and asked to take one tab/day for the first six weeks (100mg strength for two weeks then 300mg strength for four weeks) followed by two tabs/day for the remaining 18 weeks.
Participants will be given blinded medication and asked to take one tab/day for the first six weeks (100mg strength for two weeks then 300mg strength for four weeks) followed by two tabs/day for the remaining 18 weeks
Placebo Comparator: Placebo
Same number of tablets and appearance as active drug.
Same appearance/dosing as active drug.
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|Dundee, United Kingdom, DD1 9SY|
|Study Director:||Allan Struthers, MD FRCP||University of Dundee|
|Principal Investigator:||Alan J Robertson, MBChB MRCP||University of Dundee|