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

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.

Study Overview

• Status: Terminated
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Willingness to sign informed consent
3. Ability to return for follow up visits
4. 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:

1. Intolerance to thienopyridines
2. Hypersensitivity to ticagrelor or any component of the product.
3. Concomitant use of oral anticoagulation with vitamin K antagonist, factor Xa inhibitor, or direct thrombin inhibitor
4. History of intracranial hemorrhage
5. History of severe hepatic impairment defined by baseline transaminase greater than or equal to 3x ULN or any elevation in bilirubin
6. Active bleeding
7. Allergy to aspirin
8. Baseline TcPO2 < 10 mmHg post angiography
9. Resting, pre- procedure heart rate <50 beats-per-minute without a permanent pacemaker and not on an atrioventricular nodal blocking agent
10. Severe COPD on home oxygen therapy -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel; Clopidogrel 75mg by mouth daily	Drug: Clopidogrel; 75mg once a day by mouth; Other Names: Plavix
Experimental: Ticagrelor; Ticagrelor 90mg by mouth twice daily	Drug: Ticagrelor; 90mg twice a day by mouth; Other Names: Brilinta; Brilique; 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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Joseph Campbell, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): May 1, 2020
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 28, 2014
• First Posted (Estimate): September 3, 2014

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 14-799

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes