Peripheral Arterial DiseasePhase 4NCT00189618
The Effects of Physical Training, ASA (Aspirin), and Clopidogrel on the Walking Capacity of Patients With Stage II Peripheral Arterial Disease (PAD)
A Phase 4 study testing Aspirin and Clopidogrel in people with Peripheral Arterial Disease, run by Arteriogenesis Competence Network at 16 sites in 2 countries.
Trial summary
To evaluate the change in walking capacity after a well organized and structured intensive physical training program with supportive pharmacotherapy with Clopidogrel or ASA. It is hypothesized that statistically superior results will emerge from a structured training supported by Clopidogrel as compared to a… Read more about this study
- Who is it for?
- Ages 45 to 95 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Aspirin and Clopidogrel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 16 sitesin 2 countries
- Study dates
- May 2005to Jun 2008
- 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 45 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inclusion criteria for CD stability testing:
- Patients of both sexes with subjectively reported initial claudication distances between 50 and 500 m
- Patients with treadmill tested initial claudication distances between 50 and 400 m
- History of intermittent claudication > 3 months
- Established PAD diagnosis (ABI reference leg < 0.95 in non-diabetics, TBI reference leg < 0.70 in diabetics)
- CLI ruled-out (ankle pressures > 50 mmHg (non diabetics), toe pressures > 30 mmHg (diabetics))
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- Stabilized treatment of concomitant diseases
- Inclusion criteria for randomized treatment phase:
- Patients of both sexes with treadmill tested initial claudication distances between 50 and 400 m
- ICD variability during stability testing phase less than 25 %
- History of intermittent claudication > 3 months
- Established PAD diagnosis (ABI reference leg < 0.95 in non-diabetics, TBI reference leg < 0.70 in diabetics)
- CLI ruled-out (ankle pressures > 50 mmHg (non diabetics), toe pressures > 30 mmHg (diabetics))
- Stabilized treatment of concomitant diseases
- Written informed consent
Who cannot join
- Treatment with oral anticoagulants (except those cases, where the parallel treatment with a platelet aggregation inhibitor (ASA, Clopidogrel) and an oral anticoagulant is medically indicated and justified)
- Lower extremity surgical reconstruction or PTA within the last 3 months
- Age < 45 years old (M), childbearing potential (F)
- Buerger's disease
- Clinically evident peripheral polyneuropathy (sensibility to vibration < 4/8, ATR not revocable)
- Presence of orthopedic, cardiac, pulmonary, or other concomitant diseases interfering with or preventing steady walking on a treadmill
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- Clinically manifested congestive cardiac failure (NYHA class II - IV)
- Pretreatment with vasotherapeutics within the last 4 weeks prior to recruitment to the study without appropriate wash-out (> 5 half life times of the vasoactive drug)
- Consuming disease with life expectancy of less than 2 years
- Noncompliance of patient due to personality disorders or concomitant disease
- Known ASA or Clopidogrel intolerance
- Conditions requiring the regular intake of non-steroidal anti-inflammatory drugs
- Peptic ulcer within the previous 6 months
- History of GI or any other bleeding disorder within the previous 6 months
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
Switzerland10 sites
University Hospital Basel Dpt. Angiology
Basel, 4031
Ospedale San Giovanni
Bellinzona, 6500
Kantonsspital Bruderholz
Bruderholz, 4101
Kantonsspital Thurgau
Frauenfeld, 8500
University Hospital LAusanne
Lausanne, 1011
Kantonsspital Liestal
Liestal, 4410
Ospedale La Carita
Locarno, 6600
Kantonsspital Luzern
Lucerne, 6000
Kantonsspital St. Gallen
Sankt Gallen, 9007
University Hospital Zurich
Zurich, 8091
Germany6 sites
Evangelisches Krankenhaus Hubertus
Berlin, 14129
Dr. Doris Schulte
Berlin
Max Ratschow Klinik Darmstadt
Darmstadt, 64297
University Hospital Dresden
Dresden, 01307
Klinikum Karlsbad-Langensteinbach
Karlsbad, 76307
University Hospital Munich
Munich, 80337
About this study
Official title: The Effects of Physical Training, Aspirin, and Clopidogrel on the Walking Capacity of Patients With Stage II Peripheral Arterial Disease
To evaluate the change in walking capacity after a well organized and structured intensive physical training program with supportive pharmacotherapy with Clopidogrel or ASA. It is hypothesized that statistically superior results will emerge from a structured training supported by Clopidogrel as compared to a structured training supported by ASA.
Read the detailed description
Peripheral arterial disease (PAD) can not be seen in isolation but represents the peripheral manifestation of a generalized atherosclerosis. The co-morbidity with coronary heart disease and/or a cerebral atherosclerosis ranges between 20 % and 90 %, depending on the degree of severity of PAD from 1-5. The relative risk of a (predominantly cardiac) death is increased by a factor of 2 already in asymptomatic PAD patients; the risk will increase furthermore by another factor of 2 to 4 when patients become symptomatic. PAD is not a rare disease but has a prevalence of 15 % to 20 % in an elderly western population (> 50 years of age). While the clinical presentation of PAD is relatively benign in the majority of cases, the disease carries a high risk potential with high directly and indirectly related costs. Thus, from a medical but also from a socio-economic point of view, there is the need to control the PAD complication rate and related treatment costs as effectively as possible.
The most physiological treatment approach, which is internationally accepted, is physical training. There is agreement, that physical training does improve the collateralisation of vascular lesions, does improve the rheologic properties of blood, but does also lead to a shift from glycolytic (type 2) to oxidative (type 1) muscle fibers in the working musculature. This shift is associated with an increase in capillary density, a fact which subsequently favors an optimal oxygen extraction and oxygen utilisation. Another effect of physical training, which may be of utmost importance, relates to its potential to modify the patients risk factor profile. It was shown in epidemiological, clinical, and experimental studies, that even a moderate physical training does increase the insulin receptor sensitivity (and hence positively influences one of the major factors for atherosclerosis), does increase the fibrinolytic activity following prothrombotic stimulation, does decrease the diastolic blood pressure in hypertensive patients, does decrease the LDL/HDL ratio, and does decrease the overall cardiac mortality.
The aim of any treatment of intermittent claudication is a clinically relevant improvement in the patient's mobility and quality-of-life. In a previous study it was shown, that a 3 months structured, supervised PAD rehabilitation program will satisfy this demand and will lead to an improvement of the initial (painfree) claudication distance of approximately 190%. One third of the patients of this study were started on Clopidogrel as a supportive pharmacotherapy at the beginning of the trial. It was interesting to note that optimal training results (defined as an improvement of the ICD by > 200 %) were only seen in patients who were treated with Clopidogrel but were not reported from patients who received ASA (aspirin) on top of training.
Non-published data from the Art.Net. preclinical group (Dr. I. Höfer, Dr. I. Buschmann, Freiburg), which were presented at an Art.Net. meeting on March 24, 2003 showed that using a rabbit hind leg model, the magnitude of GM-CSF and MCP-1 induced arteriogenesis was reduced by approximately 40 % when ASA was co-administered; in contrast, Clopidogrel when used in the same model was neutral.
There is broad international agreement that patients with a generalized atherosclerosis and particularly patients suffering from PAD (who are at high risk for ischemic coronary and/or cerebral complications) should be treated with an antiaggregant. For pharmacoeconomic reasons the drug of choice normally is ASA.
However, following Höfer's results, ASA, although effectively preventing thrombotic complications, may hinder the arteriogenetic process required to normalize the physical capacity and QoL of PAD patients, a negative ASA effect which is not found with Clopidogrel.
Preliminary data in humans seem to support the hypothesis that in symptomatic stage II PAD patients Clopidogrel may be superior to ASA, a hypothesis which, in order to become conclusive, must be confirmed by the results of an evidence level 1 clinical trial.
(Literature at the Centre).
- Conditions
- Peripheral Arterial Disease
- Being tested
- Aspirin, Clopidogrel
- Keywords
- Peripheral vascular disease, Peripheral arterial disease, Walking Capacity, Aspirin, Clopidogrel
- Medical subject headings
- Peripheral Arterial Disease, Peripheral Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
100mg p.o. OD
ClopidogrelDrug
75mg p.o. OD
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Drug: Aspirin |
| 2 | Active comparator | Not described Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute claudication distance (ACD) change after prescription (Rx)
Measured: 3 Months
Secondary outcomes (1)
Change in daily walking activity, quality of life (QoL), initial claudication distance (ICD) change after Rx
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study startMay 2005
- Primary completionApr 2008
- Study completionJun 2008
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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arteriogenesis Competence Network
- Sponsor type
- University, hospital or other
- Investigators
- Kurt A Jaeger, MD, Prof, Principal investigator, University Hospital, Basel, SwitzerlandUlrich Hoffmann, MD, Prof, Principal investigator, University Hospital Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00189618
- Sponsor's protocol ID
- AN0104
- Status last verified
- Oct 2008
- First submitted
- 12 Sep 2005
- Last updated
- 6 Oct 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Singer E, Imfeld S, Staub D, Hoffmann U, Buschmann I, Labs KH, Jaeger KA. Effect of aspirin versus clopidogrel on walking exercise performance in intermittent claudication-a double-blind randomized multicenter trial. J Am Heart Assoc. 2012 Feb;1(1):51-6. doi: 10.1161/JAHA.111.000067. Epub 2012 Feb 20.
PubMed 23130118
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Physical Training, Aspirin, and Clopidogrel on the Walking Capacity of Patients With Stage II Peripheral Arterial Disease
- ClinicalTrials.gov ID
- NCT00189618
- Acronym / sponsor ID
- AN0104
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral vascular disease, Peripheral arterial disease, Walking Capacity, Aspirin, Clopidogrel
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Arteriogenesis Competence NetworkUniversity, hospital or other
- Study start
- May 2005
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 19 Sep 2005 (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.
To evaluate the change in walking capacity after a well organized and structured intensive physical training program with supportive pharmacotherapy with Clopidogrel or ASA. It is hypothesized that statistically superior results will emerge from a structured training supported by Clopidogrel as compared to a structured training supported by ASA.
Detailed description
Peripheral arterial disease (PAD) can not be seen in isolation but represents the peripheral manifestation of a generalized atherosclerosis. The co-morbidity with coronary heart disease and/or a cerebral atherosclerosis ranges between 20 % and 90 %, depending on the degree of severity of PAD from 1-5. The relative risk of a (predominantly cardiac) death is increased by a factor of 2 already in asymptomatic PAD patients; the risk will increase furthermore by another factor of 2 to 4 when patients become symptomatic. PAD is not a rare disease but has a prevalence of 15 % to 20 % in an elderly western population (> 50 years of age). While the clinical presentation of PAD is relatively benign in the majority of cases, the disease carries a high risk potential with high directly and indirectly related costs. Thus, from a medical but also from a socio-economic point of view, there is the need to control the PAD complication rate and related treatment costs as effectively as possible.
The most physiological treatment approach, which is internationally accepted, is physical training. There is agreement, that physical training does improve the collateralisation of vascular lesions, does improve the rheologic properties of blood, but does also lead to a shift from glycolytic (type 2) to oxidative (type 1) muscle fibers in the working musculature. This shift is associated with an increase in capillary density, a fact which subsequently favors an optimal oxygen extraction and oxygen utilisation. Another effect of physical training, which may be of utmost importance, relates to its potential to modify the patients risk factor profile. It was shown in epidemiological, clinical, and experimental studies, that even a moderate physical training does increase the insulin receptor sensitivity (and hence positively influences one of the major factors for atherosclerosis), does increase the fibrinolytic activity following prothrombotic stimulation, does decrease the diastolic blood pressure in hypertensive patients, does decrease the LDL/HDL ratio, and does decrease the overall cardiac mortality.
The aim of any treatment of intermittent claudication is a clinically relevant improvement in the patient's mobility and quality-of-life. In a previous study it was shown, that a 3 months structured, supervised PAD rehabilitation program will satisfy this demand and will lead to an improvement of the initial (painfree) claudication distance of approximately 190%. One third of the patients of this study were started on Clopidogrel as a supportive pharmacotherapy at the beginning of the trial. It was interesting to note that optimal training results (defined as an improvement of the ICD by > 200 %) were only seen in patients who were treated with Clopidogrel but were not reported from patients who received ASA (aspirin) on top of training.
Non-published data from the Art.Net. preclinical group (Dr. I. Höfer, Dr. I. Buschmann, Freiburg), which were presented at an Art.Net. meeting on March 24, 2003 showed that using a rabbit hind leg model, the magnitude of GM-CSF and MCP-1 induced arteriogenesis was reduced by approximately 40 % when ASA was co-administered; in contrast, Clopidogrel when used in the same model was neutral.
There is broad international agreement that patients with a generalized atherosclerosis and particularly patients suffering from PAD (who are at high risk for ischemic coronary and/or cerebral complications) should be treated with an antiaggregant. For pharmacoeconomic reasons the drug of choice normally is ASA.
However, following Höfer's results, ASA, although effectively preventing thrombotic complications, may hinder the arteriogenetic process required to normalize the physical capacity and QoL of PAD patients, a negative ASA effect which is not found with Clopidogrel.
Preliminary data in humans seem to support the hypothesis that in symptomatic stage II PAD patients Clopidogrel may be superior to ASA, a hypothesis which, in order to become conclusive, must be confirmed by the results of an evidence level 1 clinical trial.
(Literature at the Centre).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Aspirin |
| 2 | Active comparator | Drug: Clopidogrel |
Who may qualify
- Ages
- 45 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Inclusion criteria for CD stability testing:
- Inclusion criteria for randomized treatment phase:
Key exclusion criteria (14 listed)
- Treatment with oral anticoagulants (except those cases, where the parallel treatment with a platelet aggregation inhibitor (ASA, Clopidogrel) and an oral anticoagulant is medically indicated and justified)
- Lower extremity surgical reconstruction or PTA within the last 3 months
- Age < 45 years old (M), childbearing potential (F)
- Buerger's disease
- Clinically evident peripheral polyneuropathy (sensibility to vibration < 4/8, ATR not revocable)
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 |
|---|---|---|
| Aspirin100mg p.o. OD | Drug | 1 |
| Clopidogrel75mg p.o. OD | Drug | 2 |
Primary outcome
Absolute claudication distance (ACD) change after prescription (Rx)
Time frame: 3 Months
1 secondary outcome
Change in daily walking activity, quality of life (QoL), initial claudication distance (ICD) change after Rx
Time frame: 3 months
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 6 Oct 2008.
- Derived from this study: PubMed 23130118Singer E, Imfeld S, Staub D, Hoffmann U, Buschmann I, Labs KH, Jaeger KA. Effect of aspirin versus clopidogrel on walking exercise performance in intermittent claudication-a double-blind randomized multicenter trial. J Am Heart Assoc. 2012 Feb;1(1):51-6. doi: 10.1161/JAHA.111.000067. Epub 2012 Feb 20.
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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.
Kurt A Jaeger, MD, Prof principal investigator
University Hospital, Basel, Switzerland
Ulrich Hoffmann, MD, Prof principal investigator
University Hospital Munich
16 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aspirin and Clopidogrel in people with Peripheral Arterial Disease, run by Arteriogenesis Competence Network at 16 sites in 2 countries.
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 15 inclusion and 14 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 6 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Switzerland, Germany. 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?
Absolute claudication distance (ACD) change after prescription (Rx) (time frame: 3 Months). 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 NCT00189618, 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 6 Oct 2008.