Clinical trial NCT02762864: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: aspirin
ticagrelor
clopidogrel
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2016-05-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the effect of PRU(platelet (P2Y12) reaction units)-guided treatment on the change in

1. time of initial leg pain and time of termination of exercise test by pain, evaluated on the graded stationary bicycle test,
2. 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.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent prior to any study specific procedures.
2. Ambulatory male or female outpatients with diabetes mellitus aged 18-75 years of age or older at the time of the Screening Visit.
3. Diagnosis of PAD confirmed by history and any one of the following observed in the index (intervention) leg at the Screening Visit:

   1. Resting ABI ≤0.90, or
   2. In patients with an ABI \> 1.40 (non-compressible vessels) a resting GTI \<0.70 can be used for inclusions.
4. 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:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2. Isolated iliac and/or common femoral arteries lesion.
3. 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.
4. Gangrene or ischemic ulcer of either lower extremity.
5. PAD of a non-atherosclerotic nature.
6. Chronic oral or parenteral anticoagulant therapy (greater than 7 days)
7. Any health status that would interfere with exercise performance or prevent the patient from completion of MRI examinations.
8. Any major lower limb amputation (minor toe amputations allowed if it does not interfere with ambulation).
9. Myocardial infarction or stroke in the previous 3 months.
10. 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.
11. Not fully understanding of information pertinent to study conduct or compliance to study procedures.
12. Inability of the patient to comply with study procedures and/or followup (e.g., alcohol or drug abuse).
13. A known bleeding diathesis, hemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing.
14. 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).
15. 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).
16. Hypersensitivity to ticagrelor, aspirin or clopidogrel.
17. Pregnancy

Primary outcomes:
measure: Peak exercise time
timeFrame: month 0,12,or Early Termination
measure: Limb hemodynamics (Ankle Brachial Index or Great Toe Index)
timeFrame: month 0,1,6,12,or Early Termination
measure: leg pain MRI perfusion measures
timeFrame: month 0,4,12,or Early Termination
measure: Quality of life measures
timeFrame: month 0,12,or Early Termination
Secondary outcomes:
measure: Major lower leg events (above the ankle amputations, revascularization procedures)
timeFrame: month1, 3, 6,9,12,or Early Termination
measure: Major bleeding events
timeFrame: month1, 3, 6,9,12,or Early Termination
measure: leg pain (claudication) onset time
timeFrame: month 0,12,or Early Termination
measure: Major cardiac events (myocardial infarctions, admission due to congestive heart failure and strokes, and death)
timeFrame: month 1, 3, 6,9,12,or Early Termination
Other outcomes:
Locations:
Study officials:
affiliation: Chang Gung Memorial Hospital, Keeln\ung
name: Chi-Hsiao Yeh, MD pHD
role: PRINCIPAL_INVESTIGATOR
References: