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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02626169
Recruitment Status : Withdrawn (Pharmaceutical company sponsor withdrew support prior to enrollment of subjects.)
First Posted : December 10, 2015
Last Update Posted : December 11, 2019
Sponsor:
Information provided by (Responsible Party):
Yochai Birnbaum, Baylor College of Medicine

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.

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Study Type : Interventional  (Clinical Trial)
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 : December 2015
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Atherosclerosis

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 Name: 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 Name: Brilinta




Primary Outcome Measures :
  1. Plasma levels of 15-epi-lipoxin A4 [ Time Frame: 30 days ]
    Percent change in plasma levels of 15-epi-lipoxin A4 from baseline (%)


Secondary Outcome Measures :
  1. Plasma levels of C Reactive Protein (CRP) [ Time Frame: 30 days ]
    Percent changes in plasma CRP from baseline (%)

  2. platelet aggregation in blood sample [ Time Frame: 30 days ]
    Percentage change in inhibition of platelet aggregation in blood sample from baseline (%)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02626169


Locations
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United States, Texas
Baylor Clinic
Houston, Texas, United States, 77030
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
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Principal Investigator: Yochai Birnbaum, MD Baylor College of Medicine, Houston

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Responsible Party: Yochai Birnbaum, Professor of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02626169    
Other Study ID Numbers: H-33860
First Posted: December 10, 2015    Key Record Dates
Last Update Posted: December 11, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Yochai Birnbaum, Baylor College of Medicine:
15-epi-lipoxin A4
inflammation
atherosclerosis
Additional relevant MeSH terms:
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Atherosclerosis
Inflammation
Pathologic Processes
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Lipoxin A4
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents