Establishing the Microcirculatory Effects of Ticagrelor on Tissue Perfusion in Critical Limb Ischemia

Study Overview
=================
Brief Summary
-----------------
This is a single center, prospective, randomized, unblinded, open-label, active controlled pilot study to evaluate the efficacy and safety of ticagrelor plus aspirin versus clopidogrel plus aspirin in patients with Rutherford Stage IV to VI PAD that have undergone a percutaneous transluminal angioplasty (PTA) of the lower extremities in the past 2 weeks.

Detailed Description
-----------------
Enrollment into the study will require severe symptomatic CLI without wounds (Rutherford Stage IV) or CLI with concomitant vascular insufficiency wounds (Rutherford Stage V-VI PAD). Potential participants will be identified and screened prior to discharge or at the time of the first out-patient visit (within 2 weeks after discharge) after a percutaneous lower extremity arterial angiography with arterial intervention (stent or balloon angioplasty) for the presence of lower extremity vascular insufficiency. Participants will be classified as Rutherford Class IV - VI (with or without ulcerations). A total of 60 patients will be randomized into 2 treatment groups in a 1:1 ratio (ticagrelor to clopidogrel). Patients are placed on clopidogrel after their arterial intervention per standard of care. They will remain on clopidogrel up to the time that randomization occurs. For patients that are randomized to ticagrelor, the clopidogrel will be stopped. Patients will be randomized to either ticagrelor 90mg by mouth twice daily or clopidogrel 75mg by mouth daily.

Official Title
-----------------
Establishing the Microcirculatory Effects of Ticagrelor on Tissue Perfusion in Critical Limb Ischemia

Conditions
-----------------
Peripheral Arterial Disease

Intervention / Treatment
-----------------
* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults age 18-100 years with Rutherford Classification Stage IV through VI PAD with a recent percutaneous lower extremity arterial angiography with arterial intervention in the past 2 weeks Willingness to sign informed consent Ability to return for follow up visits A female patient of childbearing potential who is sexually active must agree to use adequate contraception from screening until 30 days after receiving the last dose of study drug. Women not of childbearing potential are defined as those who have surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who are post menopausal (defined as at least 2 years since last regular menses). The female patient should not be lactating and must have a negative pregnancy test at screening. Exclusion Criteria: Patients will be ineligible for this study if they meet any one of the following criteria: Intolerance to thienopyridines Hypersensitivity to ticagrelor or any component of the product. Concomitant use of oral anticoagulation with vitamin K antagonist, factor Xa inhibitor, or direct thrombin inhibitor History of intracranial hemorrhage History of severe hepatic impairment defined by baseline transaminase greater than or equal to 3x ULN or any elevation in bilirubin Active bleeding Allergy to aspirin Baseline TcPO2 < 10 mmHg post angiography Resting, pre- procedure heart rate <50 beats-per-minute without a permanent pacemaker and not on an atrioventricular nodal blocking agent Severe COPD on home oxygen therapy -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clopidogrel<br>Clopidogrel 75mg by mouth daily | Drug: Clopidogrel<br>* 75mg once a day by mouth<br>* Other names: Plavix;|
| Experimental: Ticagrelor<br>Ticagrelor 90mg by mouth twice daily | Drug: Ticagrelor<br>* 90mg twice a day by mouth<br>* Other names: Possia;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in TcPO2 From Baseline to Month 6 | The primary endpoint is the absolute change in TcPO2 from baseline to month 6 compared between treatment groups. | 6 months |