Back to resultsPost-operative Treatment of Diabetic Peripheral Arterial Disease Guided by Platelet Reactivity Unit
Primary Purpose
Peripheral Artery Disease
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
platelet (P2Y12) reaction units
ticagrelor
Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral Artery Disease focused on measuring aspirin, ticagrelor, clopidogrel
Eligibility Criteria
Inclusion Criteria:
- Written informed consent prior to any study specific procedures.
- Ambulatory male or female outpatients with diabetes mellitus aged 18-75 years of age or older at the time of the Screening Visit.
Diagnosis of PAD confirmed by history and any one of the following observed in the index (intervention) leg at the Screening Visit:
- Resting ABI ≤0.90, or
- In patients with an ABI > 1.40 (non-compressible vessels) a resting GTI <0.70 can be used for inclusions.
- endovascular +/- bypass surgery for superficial femoral artery and/or popliteal and/or tibial arteries, that is planned to occur within 6 weeks after the screening visit. Patients receiving concomitant iliac artery endovascular procedures may be enrolled as long as their procedure also includes treating the distal SFA, popliteal or tibial arteries. The patient is randomised after revascularization procedure has been confirmed as technically successful.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Isolated iliac and/or common femoral arteries lesion.
- Participation in other clinical study with an investigational product within the last 3 months or any new clinical trial during the course of this study.
- Gangrene or ischemic ulcer of either lower extremity.
- PAD of a non-atherosclerotic nature.
- Chronic oral or parenteral anticoagulant therapy (greater than 7 days)
- Any health status that would interfere with exercise performance or prevent the patient from completion of MRI examinations.
- Any major lower limb amputation (minor toe amputations allowed if it does not interfere with ambulation).
- Myocardial infarction or stroke in the previous 3 months.
- Any concomitant disease process with a life expectancy of less than 1 year or which is sufficiently severe as to compromise the validity of test performance.
- Not fully understanding of information pertinent to study conduct or compliance to study procedures.
- Inability of the patient to comply with study procedures and/or followup (e.g., alcohol or drug abuse).
- A known bleeding diathesis, hemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing.
- MRI examination is prohibited due to renal insufficiency or renal failure requiring dialysis. Any condition that can not receiving MRI examination, such as claustrophobia, previous abdominal aortic stent(strong artifact).
- History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days (if the surgical wound is judged to be associated with an increased risk of bleeding).
- Hypersensitivity to ticagrelor, aspirin or clopidogrel.
- Pregnancy
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
PRU-guided
non PRU-guided
Arm Description
dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patients with PRU <234 seconds and followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period. For patients in the PRU-target group with PRU ≥234 seconds, rescue medicine (ticagrelor) will be added to keep PRU<234 seconds.
dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patients with PRU <234 seconds and followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period, regardless the levels of PRU.
Outcomes
Primary Outcome Measures
Peak exercise time
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the leg peak exercise time over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Limb hemodynamics (Ankle Brachial Index or Great Toe Index)
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the Limb hemodynamics (Ankle Brachial Index or Great Toe Index) over time (pre-revascularization and at 1, 6, and 12 months post-revascularization) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
leg pain MRI perfusion measures
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the lower leg muscle GOLD perfusion measure over time (pre-revascularization, 4, and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Quality of life measures
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the quality of life over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Secondary Outcome Measures
Major lower leg events (above the ankle amputations, revascularization procedures)
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the major lower limb events, including above ankle amputation, new ulceration, and revascularization procedures over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Major bleeding events
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in bleeding events analyzed using the Thrombolysis in Myocardial Infarction Study Group (TIMI), PLATO, Bleeding Academic Research Consortium (BARC) and International Society of Thrombosis and Haemostasis (ISTH) definitions over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
leg pain (claudication) onset time
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the leg pain (claudication) onset time over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Major cardiac events (myocardial infarctions, admission due to congestive heart failure and strokes, and death)
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the major cardiac events including fatal and non-fatal myocardial infarctions, admission for congestive heart failure, and strokes, and death over time life over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02762864
Brief Title
Post-operative Treatment of Diabetic Peripheral Arterial Disease Guided by Platelet Reactivity Unit
Official Title
Post-operative Treatment of Diabetic Peripheral Arterial Disease Guided by Platelet Reactivity Unit
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
April 2019 (Anticipated)
Study Completion Date
April 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chang Gung Memorial Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To compare the effect of PRU(platelet (P2Y12) reaction units)-guided treatment on the change in
time of initial leg pain and time of termination of exercise test by pain, evaluated on the graded stationary bicycle test,
the lower limb perfusion by using MRI blood oxygenation-level dependent (BOLD) and dynamic contrast enhancement sequences and measures the extracellular volume fraction (ECV) as an indicator of fibrosis severity in calf muscles, from one to 52 weeks post-revascularization in patients with peripheral artery disease who have undergone endovascular revascularization -/+ bypass surgery for moderate to severe claudication or ischemic rest pain.
Detailed Description
Patients will be randomly assigned to PRU-guided and non-PRU-guided group. In the non-PRU -target group, dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patient followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period. In the PRU-target group, dual antiplatelet therapy will be the same protocol as in the non-PRU-target group for patients with PRU <234 seconds. However, for patients in the PRU-target group with PRU ≥234 seconds, rescue medicine will be added to keep PRU<234 seconds.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Artery Disease
Keywords
aspirin, ticagrelor, clopidogrel
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PRU-guided
Arm Type
Experimental
Arm Description
dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patients with PRU <234 seconds and followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period. For patients in the PRU-target group with PRU ≥234 seconds, rescue medicine (ticagrelor) will be added to keep PRU<234 seconds.
Arm Title
non PRU-guided
Arm Type
Active Comparator
Arm Description
dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patients with PRU <234 seconds and followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period, regardless the levels of PRU.
Intervention Type
Other
Intervention Name(s)
platelet (P2Y12) reaction units
Intervention Description
VerifyNow P2Y12 assay point-of-care testing
Intervention Type
Drug
Intervention Name(s)
ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.
Intervention Type
Drug
Intervention Name(s)
Comparator
Other Intervention Name(s)
Aspirin, Clopidogrel
Intervention Description
dual antiplatelet therapy with clopidogrel 75 mg and aspirin 100 mg daily will be continued for 6 months after the procedure for patient followed with single antiplatelet therapy with clopidogrel 75 mg daily throughout the follow-up period.
Primary Outcome Measure Information:
Title
Peak exercise time
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the leg peak exercise time over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 0,12,or Early Termination
Title
Limb hemodynamics (Ankle Brachial Index or Great Toe Index)
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the Limb hemodynamics (Ankle Brachial Index or Great Toe Index) over time (pre-revascularization and at 1, 6, and 12 months post-revascularization) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 0,1,6,12,or Early Termination
Title
leg pain MRI perfusion measures
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the lower leg muscle GOLD perfusion measure over time (pre-revascularization, 4, and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 0,4,12,or Early Termination
Title
Quality of life measures
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the quality of life over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 0,12,or Early Termination
Secondary Outcome Measure Information:
Title
Major lower leg events (above the ankle amputations, revascularization procedures)
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the major lower limb events, including above ankle amputation, new ulceration, and revascularization procedures over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month1, 3, 6,9,12,or Early Termination
Title
Major bleeding events
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in bleeding events analyzed using the Thrombolysis in Myocardial Infarction Study Group (TIMI), PLATO, Bleeding Academic Research Consortium (BARC) and International Society of Thrombosis and Haemostasis (ISTH) definitions over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month1, 3, 6,9,12,or Early Termination
Title
leg pain (claudication) onset time
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the leg pain (claudication) onset time over time (pre-revascularization and 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 0,12,or Early Termination
Title
Major cardiac events (myocardial infarctions, admission due to congestive heart failure and strokes, and death)
Description
To compare the effects of PRU-guided versus non-PRU-guided treatment on changes in the major cardiac events including fatal and non-fatal myocardial infarctions, admission for congestive heart failure, and strokes, and death over time life over time (pre-revascularization and 1, 3, 6, 9, 12 months post-revascularization, or early termination ) during 12 months of therapy in patients with Peripheral Artery Disease who have undergone endovascular -/+ bypass surgery revascularization for moderate to severe claudication or ischemic rest pain.
Time Frame
month 1, 3, 6,9,12,or Early Termination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent prior to any study specific procedures.
Ambulatory male or female outpatients with diabetes mellitus aged 18-75 years of age or older at the time of the Screening Visit.
Diagnosis of PAD confirmed by history and any one of the following observed in the index (intervention) leg at the Screening Visit:
Resting ABI ≤0.90, or
In patients with an ABI > 1.40 (non-compressible vessels) a resting GTI <0.70 can be used for inclusions.
endovascular +/- bypass surgery for superficial femoral artery and/or popliteal and/or tibial arteries, that is planned to occur within 6 weeks after the screening visit. Patients receiving concomitant iliac artery endovascular procedures may be enrolled as long as their procedure also includes treating the distal SFA, popliteal or tibial arteries. The patient is randomised after revascularization procedure has been confirmed as technically successful.
Exclusion Criteria:
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
Isolated iliac and/or common femoral arteries lesion.
Participation in other clinical study with an investigational product within the last 3 months or any new clinical trial during the course of this study.
Gangrene or ischemic ulcer of either lower extremity.
PAD of a non-atherosclerotic nature.
Chronic oral or parenteral anticoagulant therapy (greater than 7 days)
Any health status that would interfere with exercise performance or prevent the patient from completion of MRI examinations.
Any major lower limb amputation (minor toe amputations allowed if it does not interfere with ambulation).
Myocardial infarction or stroke in the previous 3 months.
Any concomitant disease process with a life expectancy of less than 1 year or which is sufficiently severe as to compromise the validity of test performance.
Not fully understanding of information pertinent to study conduct or compliance to study procedures.
Inability of the patient to comply with study procedures and/or followup (e.g., alcohol or drug abuse).
A known bleeding diathesis, hemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing.
MRI examination is prohibited due to renal insufficiency or renal failure requiring dialysis. Any condition that can not receiving MRI examination, such as claustrophobia, previous abdominal aortic stent(strong artifact).
History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days (if the surgical wound is judged to be associated with an increased risk of bleeding).
Hypersensitivity to ticagrelor, aspirin or clopidogrel.
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chi-Hsiao Yeh, MD pHD
Organizational Affiliation
Chang Gung Memorial Hospital, Keeln\ung
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Post-operative Treatment of Diabetic Peripheral Arterial Disease Guided by Platelet Reactivity Unit
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