Walking Effect of Long Term Ticagrelor in Subjects With PAD Who Have Undergone EVR
Condition: Peripheral Artery Disease (PAD)
MeSH terms: Peripheral Arterial Disease
Intervention: Ticagrelor; Comparator
Intervention description: Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.; Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures
Intervention MeSH terms: Ticagrelor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 50 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Myocardial Infarction; Peripheral Arterial disease; Mycardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Altherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ticagrelor; Ticlopidine; Platelet Aggregation inhibitors; Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Purinegic P2Y Receptor Antagonists; Purinegic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Actions; Physiological Effects of Drugs; Fibrinolytic Agents; Crardiovascular Agents

Summary:

      To compare the effect of ticagrelor versus aspirin on the change in peak walking time,
      evaluated on the graded treadmill test, from one to 26 weeks post-revascularization in
      patients with peripheral artery disease who have undergone endovascular revascularization for
      moderate to severe claudication or ischemic rest pain.
    

Eligibility criteria:

        Inclusion Criteria

          1. Written informed consent prior to any study specific procedures.

          2. Ambulatory male or female outpatients aged 50 years of age or older at the time of the
             Screening Visit.

          3. EVR, below the inguinal ligament that includes the distal SFA and/or popliteal and/or
             tibial arteries, that is planned to occur within 5 weeks after the Screening Visit, as
             determined and clearly documented by the Principal Investigator or physician
             Sub-Investigator (MD/DO). Patients undergoing a proximal revascularization may be
             enrolled as long as their procedure also includes treating the distal SFA, popliteal
             or tibial arteries. The EVR must be confirmed as technically successful (a completed
             procedure where haemostasis has been achieved) before the patient is randomised.

          4. Normal inflow into the lower extremity as determined by the Principal Investigator or
             physician Sub-Investigator (MD/DO). Adequacy of inflow can be assessed by hemodynamic
             measures, angiography or other imaging modalities obtained during Screening or
             recorded in the medical records up to 30 days prior to the Screening Visit or as
             defined by imaging at the time of the procedure. A patient with inadequate inflow at
             the time of Screening can still be enrolled if the inflow is addressed and resolved by
             the planned revascularization procedure.

          5. 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.

          6. Patient has been advised of the beneficial effects of smoking cessation and exercise
             therapy but is not in the process of changing their smoking status or exercise at the
             time of the Screening Visit.

        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. Revascularisation planned only to treat proximal (inflow) disease in the iliac and/or
             common femoral arteries.

          3. Previous randomisation in the present study.

          4. Participation in another clinical study with an investigational product within the
             last 3 months or any new clinical trial during the course of this study.

          5. Gangrene or ischemic ulcer of either lower extremity.

          6. PAD of a non-atherosclerotic nature.

          7. Clinical necessity to use dual antiplatelet therapy within 7 days prior to
             randomisation, or single anti-platelet therapy (ticlopidine, prasugrel, vorapaxar,
             ticagrelor or dipyridamole) other than clopidogrel or aspirin. Clopidogrel or aspirin
             can be taken up to and including the time that the loading dose is being given.

          8. Clinical necessity to use the following restricted concomitant medications within 4
             weeks prior to randomisation. Patients taking any of these medications at the
             Screening Visit may be considered for randomisation after a 4 week washout period from
             the medication.

               1. Pentoxifylline or cilostazol for relief of claudication symptoms

               2. Chronic oral or parenteral anticoagulant therapy (greater than 7 days)

               3. Strong inhibitors of CYP3A enzymes (Section 5.6.9.1)

               4. Strong inducers of CYP3A enzymes (Section 5.6.9.2)

               5. Simvastatin or lovastatin at daily doses over 40 mg

          9. Any disease process (e.g. angina, cardiac abnormality, congestive heart failure (CHF),
             chronic obstructive pulmonary disease (COPD), respiratory disease, obesity, stroke,
             severe neuropathy of the foot, symptomatic musculoskeletal disease of the lower
             extremity), other than PAD, that would interfere with exercise performance during the
             ETT or prevent the patient from reaching their claudication-limited PWT as the primary
             endpoint of the study.

         10. Coronary, aortic surgery, angioplasty, lumbar sympathectomy or lower extremity surgery
             that impacts the ability to walk on a treadmill within the past 3 months prior to EVR.
             Revascularization of the non-index lower extremity within the past 4 weeks prior to
             EVR.

         11. Any major lower limb amputation due to PAD anticipated within the next 3 months or
             prior major amputation due to PAD (minor toe amputations allowed if it does not
             interfere with ambulation).

         12. Myocardial infarction or stroke in the previous 3 months.

         13. 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.

         14. Dementia likely to jeopardise understanding of information pertinent to study conduct
             or compliance to study procedures.

         15. Concern for the inability of the patient to comply with study procedures and/or
             followup (e.g., alcohol or drug abuse).

         16. Resting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥95 mmHg at the
             Screening Visit, in spite of antihypertensive treatments allowed by the protocol.

         17. A known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding,
             whether resolved or ongoing.

         18. Known severe liver disease (e.g., ascites and or clinical signs of coagulopathy).

         19. Renal failure requiring dialysis.

         20. 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).

         21. History of thrombocytopenia or neutropenia.

         22. Hypersensitivity to ticagrelor, aspirin or lactose.

         23. Initiation of antidiabetic, antihypertensive, lipid-lowering and beta-blocking drugs
             within 1 month prior to the Screening Visit.

         24. Pregnancy, lactation, fertility without protection against pregnancy (for women of
             childbearing potential; a urine or serum pregnancy test will be performed at the
             Screening Visit).