Walking Effect of Long Term Ticagrelor in Subjects With PAD Who Have Undergone EVR

Peripheral Artery Disease (PAD) Clinical Trial

— TI-PAD EVR  

Official title:

A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients With Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02227368
• Other study ID #: D5135L00003
• Status: Terminated
• Phase: Phase 2
• First received: August 19, 2014
• Last updated: June 10, 2016
• Start date: October 2014
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

A Phase II Multicentre, Randomised, Double-Blind, Controlled, Parallel-Group Study to Evaluate the Walking Time Effect of Long-Term Ticagrelor in Comparison to Long-Term Aspirin Administration in Ambulatory Patients with Peripheral Artery Disease Undergoing Endovascular Revascularization - The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study TI-PAD I EVR

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 71
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 130 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Artery Disease (PAD)

Intervention

Drug:
• Ticagrelor
Antiplatelet therapy approved for ACS. Antagonist of P2Y12 and inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation.
• Comparator
Aspirin monotherapy anti-platelet treatment for PAD patients following EVR procedures

Locations

Country	Name	City	State
United States	Research Site	Cleveland	Ohio
United States	Research Site	Daytona Beach	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	McKinney	Texas
United States	Research Site	Munster	Indiana
United States	Research Site	New York	New York
United States	Research Site	Ocala	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Sarasota	Florida
United States	Research Site	Yonkers	New York

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	CPC Clinical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peak walking time at Week 26 compared to the Week 1 baseline visit	To compare the effect of ticagrelor versus aspirin on the change in peak walking time (PWT), evaluated on the graded treadmill test, from one to 26 weeks post-endovascular revascularization (EVR) in patients with peripheral artery disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Week 1 to Week 26	No
Secondary	Peak walking time	Time course of change from Week 1 Baseline to Week 4 and 13, or early termination in PWT.	Week 1,4,13, 26 or Early Termination	No
Secondary	Claudication onset time	To compare the effects of ticagrelor versus aspirin on changes in the claudication onset time over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13 , 26 or Early Termination	No
Secondary	Limb hemodynamics (Ankle Brachial Index or Great Toe Index)	To compare the effects of ticagrelor versus aspirin on changes in the Limb hemodynamics (Ankle Brachial Index or Great Toe Index) over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No
Secondary	Quality of life measures	To compare the effects of ticagrelor versus aspirin on changes in the Quality of life measures over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No
Secondary	Rutherford clinical classification	To compare the effects of ticagrelor versus aspirin on changes in the Rutherford clinical classification over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No
Secondary	Major cardiac events including fatal and non-fatal myocardial infarctions and strokes, and vascular death	To compare the effects of ticagrelor versus aspirin on changes in the major cardiac events including fatal and non-fatal myocardial infarctions and strokes, and vascular death over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No
Secondary	Limb events including above the ankle amputations or any revascularization procedures in either lower extremity	To compare the effects of ticagrelor versus aspirin on changes in the limb events including above the ankle amputations or any revascularization procedures in either lower extremity over time (pre-revascularization and at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No
Secondary	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	To compare the effects of ticagrelor versus aspirin on changes in the 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 at 1, 4, 13, and 26 weeks post-revascularization) during 26 weeks of therapy in patients with Peripheral Artery Disease who have undergone endovascular revascularization for moderate to severe claudication or ischemic rest pain.	Weeks 1, 4, 13, 26 or Early Termination	No