The Effect of Ticagrelor on 15-Epi-Lipoxin A4 and Inflammation

Sponsor

Baylor College of Medicine (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02626169

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ticagrelor and clopidogrel are FDA-approved drugs for inhibition of platelet hyper-reactivity in certain clinical situations. The platelet inhibition and patient outcomes (PLATO) trial showed that in patients with acute coronary syndromes, ticagrelor significantly reduced the primary endpoint (cardiovascular death, myocardial infarction or stroke), all-cause mortality and cardiovascular mortality compared to clopidogrel. It has been suggested that in addition to its anti-platelet effects, ticagrelor has additional unique effects, including anti-inflammatory effects that are not shared by clopidogrel. In the present study the investigators will assess whether ticagrelor, as compared to clopidogrel, increases serum levels of 15-epi-lipoxin A4, a potent endogenous anti-inflammatory mediator.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Clopidogrel Drug: Ticagrelor	Phase 4

Detailed Description

Clopidogrel, ticagrelor and prasugrel are routinely used for platelet inhibition in addition to aspirin in patients after acute coronary syndromes. The platelet inhibition and patient outcomes (PLATO) trial showed that in patients with acute coronary syndromes, ticagrelor significantly reduced the primary endpoint (cardiovascular death, myocardial infarction or stroke), all-cause mortality and cardiovascular mortality compared to clopidogrel. On the other hand, when compared with clopidogrel in patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy did not affect overall mortality despite the fact that it was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. This may suggest that ticagrelor possesses additional (pleiotropic) effects besides platelet inhibition.

The investigators have recently shown that pioglitazone increases 15-epi-lipoxin A4 blood levels in patients. The investigators have recently found that in the rat, ticagrelor increases tissue levels of 15-epi-lipoxin A4 in the heart, aorta and kidney.

It is plausible that some of the favorable effects of ticagrelor seen in the clinical studies are mediated via the anti-inflammatory effects of 15-epi-lipoxin A4.

15-epi-lipoxin A4 is a potent anti-inflammatory and inflammation-resolving mediator derived from arachidonic acid. Several studies have suggested that ticagrelor has anti-inflammatory properties in various animal models. In the present study the investigators will assess if ticagrelor increases blood 15-epi-lipoxin A4 levels at doses used in patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effect of Ticagrelor on 15-Epi-Lipoxin A4 and Inflammation

Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2018

Anticipated Study Completion Date :

Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clopidogrel Clopidogrel 75 mg once a day by mouth for 30 days	Drug: Clopidogrel Clopidogrel 75 mg once a day by mouth for 30 days Other Names: Plavix
Active Comparator: Ticagrelor Ticagrelor 90 mg twice daily by mouth for 30 days	Drug: Ticagrelor Ticagrelor 90 mg twice daily by mouth for 30 days Other Names: Brilinta

Arm

Intervention/Treatment

Active Comparator: Clopidogrel

Clopidogrel 75 mg once a day by mouth for 30 days

Drug: Clopidogrel

Clopidogrel 75 mg once a day by mouth for 30 days

Other Names:

Plavix

Active Comparator: Ticagrelor

Ticagrelor 90 mg twice daily by mouth for 30 days

Drug: Ticagrelor

Ticagrelor 90 mg twice daily by mouth for 30 days

Other Names:

Brilinta

Outcome Measures

Primary Outcome Measures

Plasma levels of 15-epi-lipoxin A4 [30 days]
Percent change in plasma levels of 15-epi-lipoxin A4 from baseline (%)

Secondary Outcome Measures

Plasma levels of C Reactive Protein (CRP) [30 days]
Percent changes in plasma CRP from baseline (%)
platelet aggregation in blood sample [30 days]
Percentage change in inhibition of platelet aggregation in blood sample from baseline (%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures

Women of childbearing potential must be using an acceptable method of contraception to avoid pregnancy throughout the study

Patients with stable coronary artery disease (3-12 months after Acute Coronary Syndrome) who receive clopidogrel for at least 3 months.

Exclusion Criteria:

Recent stroke or acute coronary syndromes (<3 months before randomization).

Concurrent use of aspirin >100 mg/day where the dose reduction to 81 mg/day is contraindicated.

Current use of theophylline.

Concurrent use of Non Steroidal Anti-Inflammatory Drugs.

Patients receiving the following medications: ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, telithromycin, rifampin, dexamethasone, phenytoin, carbamazepine, or phenobarbital. Patients receiving simvastatin or lovastatin at doses greater than 40 mg daily.

Patients with type 2 diabetes with a fasting plasma glucose greater than 200 mg/dl.

Active inflammatory disease or chronic infection.

Contraindication for aspirin, clopidogrel or ticagrelor.

Women who are pregnant or breastfeeding.