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Effect of Ticagrelor Versus Clopidogrel on Endothelial Dysfunction and Vascular Inflammation

Primary Purpose

Endothelial Dysfunction, Vascular Inflammation

Status

Unknown status

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Ticagrelor

Clopidogrel

About this trial

This is an interventional treatment trial for Endothelial Dysfunction

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures
Men and women ≥20 years of age
Documented history of non-ST-segment acute coronary syndrome occurring 30 ~ 365 days prior to randomization and successfully treated with percutaneous coronary intervention using drug-eluting stent
Patient currently prescribed and tolerating aspirin 100mg and clopidogrel 75mg.
Patient who have demonstrated endothelial dysfunction defined as percent flow-mediated dilation values lower than 7% at baselines test

Exclusion Criteria:

Patients with angina related symptoms
Patients who did not undergo or failed invasive treatment
Patients with a history of hypersensitivity to ticagrelor or clopidogrel
Patients who took an anti-coagulant, anti-thrombotic regularly before the study, or plan to have continuous treatment during the study
Patients who took vasoactive agents or caffeine ingestion for <48
Patients with decompensated congestive heart failure of cardiogenic shock (Killip classification III or IV)
Patients with intractable arrhythmia
Patients with intractable arrhythmia
Patients with second or third degree atrioventricular block
Patients with uncontrolled hypertension
Patients with high risk of hemorrhage like blood coagulation disorders, gastrointestinal bleeding, gross hematuria, intraocular bleeding, hemorrhagic stroke, intracranial hemorrhage
Patients with more than moderate chronic obstructive pulmonary disease diagnosed by symptoms or documented by pulmonary function test
Patients who required renal replacement therapy
Patients with moderate to severe hepatic impairment
Patients with platelet <100,000/μL
Patients with hematocrit <30%
Concomitant oral or parenteral therapy with strong cytochrome P450 3A4 inhibitors, cytochrome P450 3A substrates with narrow therapeutic indices, or strong cytochrome P450 3A4 inducers i) Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice ii) Substrates with narrow therapeutic index: cyclosporine, quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily iii) Strong inducers: rifampin/rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital
Patient who need to take drugs other than study medications and allowed concomitant medications during study period.
Patients who have planned elective surgery or invasive procedure requiring temporary discontinued study medication during study period.
Patients who are pregnant, breast feeding and not using medically acceptable birth control.
Patients considered as unsuitable based on medical judgment by investigators.

Sites / Locations

Seoul St. Mary's Hospital, The Catholic University of KoreaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor

Clopidogrel

Arm Description

Ticagrelor 90mg twice daily

Clopidogrel 75mg once daily

Outcomes

Primary Outcome Measures

Change in percent flow-mediated dilation (FMD) values

Secondary Outcome Measures

Percent flow-mediated dilation (FMD) values

Incidence rate of patient with percent flow-mediated dilation (FMD) value less than 7%

Inflammatory gene expression levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR)

Full Information

NCT ID

NCT02379676

First Posted

February 28, 2015

Last Updated

July 3, 2016

Sponsor

Kiyuk Chang

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02379676

Brief Title

Effect of Ticagrelor Versus Clopidogrel on Endothelial Dysfunction and Vascular Inflammation

Official Title

Comparison of the Effects of Ticagrelor Versus Clopidogrel on Endothelial Dysfunction and Vascular Inflammation in Patients With Prior Non-ST-segment Acute Coronary Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Unknown status

Study Start Date

January 2015 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

March 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kiyuk Chang

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to compare the effects of ticagrelor and clopidogrel on endothelial dysfunction and vascular inflammation Ticagrelor will lead to beneficial pleiotropic effects compared with treatment with clopidogrel in patients receiving a drug-eluting stents (DES) during percutaneous coronary intervention (PCI) for non-ST-segment acute coronary syndrome (NSTE-ACS) beyond 1 month after the index event. Ticagrelor treatment will improve percent flow-mediated dilation (FMD) values and reduces inflammatory gene expression on peripheral blood mononuclear cells.

Detailed Description

The primary objective of this study lies in whether ticagrelor improves endothelial dysfunction compared to clopidogrel, measured by endothelium-dependent flow-mediated dilation (FMD). The secondary objective is to demonstrate whether ticagrelor has an anti-atherosclerotic effect compared to clopidogrel in terms of reducing systemic low-grade inflammation. Endpoints are 1) difference of flow-mediated dilation values, and 2) messenger ribonucleic acid (mRNA) expression measured by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) of inflammation-associated key genes in circulation monocytes between non-ST-segment acute coronary syndrome patients treated with ticagrelor and clopidogrel. Patients who agree to participate study are screened at Visit 1 (30 ~ 365 days after index percutaneous coronary intervention). Patients with endothelial dysfunction defined as screening flow-mediated dilation are randomly assigned at Visit 2 (0~7 days after screening test). And then, patients should receive study drugs according to allocated groups from the day of randomization. Ticagrelor 90mg twice daily or clopidogrel 75mg daily will be maintained for 30 days. Flow-mediated dilation are performed at screening and at Visit 3 (day 30 from the treatment of study drugs) and blood sampling are performed before the first dose of study drugs at Visit 2 and at Visit 3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endothelial Dysfunction, Vascular Inflammation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor

Arm Type

Experimental

Arm Description

Ticagrelor 90mg twice daily

Arm Title

Clopidogrel

Arm Type

Active Comparator

Arm Description

Clopidogrel 75mg once daily

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Intervention Description

Ticagrelor 90mg twice daily for 30 days

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Intervention Description

Clopidogrel 75mg once daily for 30 days

Primary Outcome Measure Information:

Title

Change in percent flow-mediated dilation (FMD) values

Time Frame

Baseline, 30 days

Secondary Outcome Measure Information:

Title

Percent flow-mediated dilation (FMD) values

Time Frame

Baseline, 30 days

Title

Incidence rate of patient with percent flow-mediated dilation (FMD) value less than 7%

Time Frame

Baseline, 30 days

Title

Inflammatory gene expression levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR)

Time Frame

Baseline, 30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of informed consent prior to any study specific procedures Men and women ≥20 years of age Documented history of non-ST-segment acute coronary syndrome occurring 30 ~ 365 days prior to randomization and successfully treated with percutaneous coronary intervention using drug-eluting stent Patient currently prescribed and tolerating aspirin 100mg and clopidogrel 75mg. Patient who have demonstrated endothelial dysfunction defined as percent flow-mediated dilation values lower than 7% at baselines test Exclusion Criteria: Patients with angina related symptoms Patients who did not undergo or failed invasive treatment Patients with a history of hypersensitivity to ticagrelor or clopidogrel Patients who took an anti-coagulant, anti-thrombotic regularly before the study, or plan to have continuous treatment during the study Patients who took vasoactive agents or caffeine ingestion for <48 Patients with decompensated congestive heart failure of cardiogenic shock (Killip classification III or IV) Patients with intractable arrhythmia Patients with intractable arrhythmia Patients with second or third degree atrioventricular block Patients with uncontrolled hypertension Patients with high risk of hemorrhage like blood coagulation disorders, gastrointestinal bleeding, gross hematuria, intraocular bleeding, hemorrhagic stroke, intracranial hemorrhage Patients with more than moderate chronic obstructive pulmonary disease diagnosed by symptoms or documented by pulmonary function test Patients who required renal replacement therapy Patients with moderate to severe hepatic impairment Patients with platelet <100,000/μL Patients with hematocrit <30% Concomitant oral or parenteral therapy with strong cytochrome P450 3A4 inhibitors, cytochrome P450 3A substrates with narrow therapeutic indices, or strong cytochrome P450 3A4 inducers i) Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice ii) Substrates with narrow therapeutic index: cyclosporine, quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily iii) Strong inducers: rifampin/rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital Patient who need to take drugs other than study medications and allowed concomitant medications during study period. Patients who have planned elective surgery or invasive procedure requiring temporary discontinued study medication during study period. Patients who are pregnant, breast feeding and not using medically acceptable birth control. Patients considered as unsuitable based on medical judgment by investigators.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kiyuk Chang, MD, PhD

Phone

82-2-2258-1139

kiyuk@catholic.ac.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Sungmin Lim, MD

Phone

82-2-2258-1139

sungmin@catholic.ac.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kiyuk Chang, MD, PhD

Organizational Affiliation

Seoul St. Mary's Hospital, The Catholic.University of Korea

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul St. Mary's Hospital, The Catholic University of Korea

City

Seoul

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kiyuk Chang, MD, PhD

Phone

82-2-2258-1139

kiyuk@catholic.ac.kr

First Name & Middle Initial & Last Name & Degree

Sungmin Lim, MD

Phone

82-2-2258-1139

sungmin@catholic.ac.kr

First Name & Middle Initial & Last Name & Degree

Kiyuk Chang, MD, PhD

First Name & Middle Initial & Last Name & Degree

Sungmin Lim, MD

First Name & Middle Initial & Last Name & Degree

Eun Ho Choo, MD

12. IPD Sharing Statement

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Effect of Ticagrelor Versus Clopidogrel on Endothelial Dysfunction and Vascular Inflammation

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