Peripheral Arterial DiseasePhase 4APOSA-PADNCT01147705
Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease
A Phase 4 study testing Allopurinol in people with Peripheral Arterial Disease, run by University of Dundee at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Allopurinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2011to Jul 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- stable peripheral arterial disease (demonstrated by having a reproducible pain free walking distance on 2 consecutive treadmill tests, i.e. less than 25% variance with the reason for termination of the treadmill test must be claudication pain only)
Who cannot join
- rest pain
- childbearing potential
- heart failure
- any other exercise limiting cardiac disease
- BP > 180/100 mHg
- eGFR < 60 ml/min
Show all 11Show fewer
- liver disease
- malignancy
- already on allopurinol or had an adverse reaction to it
- recent marked change in symptoms or recent (in the last six months) intervention for PAD
- receiving treatment with either 6-mercaptopurine, azathioprine, warfarin, or theophylline
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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).
Read the detailed description
The investigators will recruit 50 patients with peripheral arterial disease for a randomised, double-blind, placebo-controlled parallel group study to see if allopurinol prolongs time to leg pain and maximum walking distance as assessed by treadmill testing and the six minute walk test. Recruitment will take place in Dundee, i.e. a single-centre trial. Treatment will last for 24 weeks.
Participants will be recruited from current and past attendees at the vascular laboratory and both the intermittent claudication clinic and other outpatient clinics at Ninewells.
Participants will be allowed to continue all their usual medication throughout. After two baseline treadmill tests, they will be randomised to either allopurinol or placebo in a parallel group study and in a double blind fashion. Each participant will be on-study for 24 weeks (which is the standard time for all PAD medical intervention trials). The ultimate dose of allopurinol will be 300 mg BD, which is the dose known to work in angina. However, for safety purposes, the initial dose will be 100 mg/day for two weeks, rising to 300 mg/day for four weeks, followed by 600 mg/day for the next 18 weeks. Participants and their bloods (UE, LFT, FBC) will be monitored at weeks 0, 6, 18 and 24 weeks and medication stopped or reduced in dose if concerns arise. If study drug dose is reduced, they will stay in study. If study drug needs to be stopped, they will stay in study in order to do an "intention to treat" analysis.
Double blind medication (allopurinol or placebo) will be prepared and packaged by Tayside Pharmaceuticals. The medication will come labelled as "Participant 1", "Participant 2", etc. and will be distributed to the participant by the research fellow according to their sequence number. The blinded treatment code will be kept by the Clinical Trials Pharmacy Department, Ninewells, who operate a 24 hour emergency unblinding facility (as necessary) and in a sealed envelope in a locked fireproof cabinet accessible by a responsible member of University of Dundee staff not directly involved in the study.
The following is the programme of visits involved in this study (list taken from the participant information sheet) -
- Visit 1 (week 0) - screening visit 1
- Consent - answer any outstanding questions you may have and complete the consent form.
- Measurement of blood pressure in arms and legs
- Treadmill test
- Blood samples
- Visit 2 (week 0) - screening visit 2
- Treadmill test - if this is stable and similar to the previous test then you are able to continue in the study
- Six minute walk test
- Measurement of blood vessel 'stiffness'
- Supply of initial study medication along with instructions.
- Two questionnaires - Walking Impairment and Quality of Life
- Visit 3 (week 6) - progress visit
- Check how you are doing on the medications
- Blood samples
- Supply of study medication for the remainder of the study
- Visit 4 (week 12) - progress visit
- Treadmill test
- Six minute walk test
- Check how you are doing on the medications
- Two questionnaires - Walking Impairment and Quality of Life
- Visit 5 (week 18) - progress visit
- Measurement of blood vessel 'stiffness'
- Check how you are doing on the medications
- Blood samples
- Visit 6 (week 24) - final visit
- Measurement of blood vessel 'stiffness'
- Treadmill test
- Six minute walk test
- Measurement of blood pressure in arms and legs
- Check how you are doing on the medications
- Blood samples
- Two questionnaires - Walking Impairment and Quality of Life
- Conditions
- Peripheral Arterial Disease
- Being tested
- Allopurinol, Placebo
- Keywords
- Peripheral arterial disease, Allopurinol
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
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
PlaceboDrug
Same appearance/dosing as active drug.
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol | Active comparator | 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. Receives: Drug: Allopurinol |
| Placebo | Placebo comparator | Same number of tablets and appearance as active drug. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Onset of claudication pain
Our primary endpoint will be the distance to onset of claudication pain at 24 weeks but we will also measure total exercise distance.
Measured: 24 weeks
Secondary outcomes (2)
Quality of life
To see if allopurinol improves quality of life in patients with PAD.
Measured: 24 weeks
Anti-oxidant effects
To investigate the anti-oxidant effects of allopurinol of patients with PAD.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study startFeb 2011
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Tayside, British Heart Foundation
- Responsible party
- Principal investigator, Alan Robertson, University of Dundee
- Investigators
- Allan Struthers, MD FRCP, Study director, University of DundeeAlan J Robertson, MBChB MRCP, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01147705
- Sponsor's protocol ID
- 2009CV16
- Other IDs
- 2010-020662-23
- Acronym
- APOSA-PAD
- Status last verified
- May 2017
- First submitted
- 18 Jun 2010
- Last updated
- 2 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Robertson AJ, Struthers AD. A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease. Can J Cardiol. 2016 Feb;32(2):190-6. doi: 10.1016/j.cjca.2015.05.010. Epub 2015 May 19.
PubMed 26277090
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allopurinol as a Possible Oxygen Sparing Agent During Exercise in Peripheral Arterial Disease
- ClinicalTrials.gov ID
- NCT01147705
- Acronym / sponsor ID
- APOSA-PAD / 2009CV16
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral arterial disease, Allopurinol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- NHS Tayside, British Heart Foundation
- Study start
- Feb 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 22 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The investigators will recruit 50 patients with peripheral arterial disease for a randomised, double-blind, placebo-controlled parallel group study to see if allopurinol prolongs time to leg pain and maximum walking distance as assessed by treadmill testing and the six minute walk test. Recruitment will take place in Dundee, i.e. a single-centre trial. Treatment will last for 24 weeks.
Participants will be recruited from current and past attendees at the vascular laboratory and both the intermittent claudication clinic and other outpatient clinics at Ninewells.
Participants will be allowed to continue all their usual medication throughout. After two baseline treadmill tests, they will be randomised to either allopurinol or placebo in a parallel group study and in a double blind fashion. Each participant will be on-study for 24 weeks (which is the standard time for all PAD medical intervention trials). The ultimate dose of allopurinol will be 300 mg BD, which is the dose known to work in angina. However, for safety purposes, the initial dose will be 100 mg/day for two weeks, rising to 300 mg/day for four weeks, followed by 600 mg/day for the next 18 weeks. Participants and their bloods (UE, LFT, FBC) will be monitored at weeks 0, 6, 18 and 24 weeks and medication stopped or reduced in dose if concerns arise. If study drug dose is reduced, they will stay in study. If study drug needs to be stopped, they will stay in study in order to do an "intention to treat" analysis.
Double blind medication (allopurinol or placebo) will be prepared and packaged by Tayside Pharmaceuticals. The medication will come labelled as "Participant 1", "Participant 2", etc. and will be distributed to the participant by the research fellow according to their sequence number. The blinded treatment code will be kept by the Clinical Trials Pharmacy Department, Ninewells, who operate a 24 hour emergency unblinding facility (as necessary) and in a sealed envelope in a locked fireproof cabinet accessible by a responsible member of University of Dundee staff not directly involved in the study.
The following is the programme of visits involved in this study (list taken from the participant information sheet) -
- Visit 1 (week 0) - screening visit 1
- Consent - answer any outstanding questions you may have and complete the consent form.
- Measurement of blood pressure in arms and legs
- Treadmill test
- Blood samples
- Visit 2 (week 0) - screening visit 2
- Treadmill test - if this is stable and similar to the previous test then you are able to continue in the study
- Six minute walk test
- Measurement of blood vessel 'stiffness'
- Supply of initial study medication along with instructions.
- Two questionnaires - Walking Impairment and Quality of Life
- Visit 3 (week 6) - progress visit
- Check how you are doing on the medications
- Blood samples
- Supply of study medication for the remainder of the study
- Visit 4 (week 12) - progress visit
- Treadmill test
- Six minute walk test
- Check how you are doing on the medications
- Two questionnaires - Walking Impairment and Quality of Life
- Visit 5 (week 18) - progress visit
- Measurement of blood vessel 'stiffness'
- Check how you are doing on the medications
- Blood samples
- Visit 6 (week 24) - final visit
- Measurement of blood vessel 'stiffness'
- Treadmill test
- Six minute walk test
- Measurement of blood pressure in arms and legs
- Check how you are doing on the medications
- Blood samples
- Two questionnaires - Walking Impairment and Quality of Life
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allopurinol | Active comparator | Drug: AllopurinolParticipants 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 | Placebo comparator | Drug: PlaceboSame number of tablets and appearance as active drug. |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- stable peripheral arterial disease (demonstrated by having a reproducible pain free walking distance on 2 consecutive treadmill tests, i.e. less than 25% variance with the reason for termination of the treadmill test must be claudication pain only)
Key exclusion criteria (11 listed)
- rest pain
- childbearing potential
- heart failure
- any other exercise limiting cardiac disease
- BP > 180/100 mHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopurinolParticipants 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 | Drug | Allopurinol |
| PlaceboSame appearance/dosing as active drug. | Drug | Placebo |
Primary outcome
Onset of claudication pain
Time frame: 24 weeks
Our primary endpoint will be the distance to onset of claudication pain at 24 weeks but we will also measure total exercise distance.
2 secondary outcomes
Quality of life
Time frame: 24 weeks
Anti-oxidant effects
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2017.
- Results publication: PubMed 26277090Robertson AJ, Struthers AD. A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease. Can J Cardiol. 2016 Feb;32(2):190-6. doi: 10.1016/j.cjca.2015.05.010. Epub 2015 May 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan Struthers, MD FRCP study director
University of Dundee
Alan J Robertson, MBChB MRCP principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Allopurinol in people with Peripheral Arterial Disease, run by University of Dundee at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Onset of claudication pain (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01147705, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2017.