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The Effect of Ticagrelor or Clopidogrel on Endothelial Function During Acute and Chronic Treatment

Primary Purpose

Ischemia

Status

Completed

Phase

Phase 4

Locations

Austria

Study Type

Interventional

Intervention

Ticagrelor

Clopidogrel

About this trial

This is an interventional treatment trial for Ischemia

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male subjects; 18 - 40 years of age
Body mass index between 18 and 27 kg/m2
Written informed consent
Normal findings in medical & bleeding history
Non-smoking

Exclusion Criteria:

Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease)
Known disorders with increased bleeding risk (e.g. peridontosis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer)
Known sensitivity to common causes of bleeding (e.g. nasal)
History of thromboembolism
History of occlusive vascular diseases
History of vascular anomalies
Impaired liver function (AST, ALT, gGT, bilirubin >2 x ULN)
Impaired renal function (serum creatinine > 1.3 mg/dl)
Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis
HIV-1/2-Ab, HbsAg or HCV-Ab positive serology
Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg
Known allergy against any test agent under study
Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol
Participation in another clinical trial during the preceding 3 weeks

Sites / Locations

Medical University of Vienna, Department of Clinical Pharmacology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Ticagrelor

Clopidogrel

Arm Description

Loading dose of 180 mg on day one, followed by a regular intake (90 mg twice daily) for 14 days

Loading dose of 600 mg on day one, followed by a regular intake (75 mg once daily) for 14 days

Outcomes

Primary Outcome Measures

Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholin (ACh) induced vasodilatation

To test the effect of ticagrelor or clopidogrel on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia.

Secondary Outcome Measures

Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceroltrinitrate (GTN) induced vasodilatation

To test the effect of ticagrelor or clopidogrel on GTN-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia.

(Expected) Peak plasma concentration of ticagrelor or clopidogrel

Full Information

NCT ID

NCT02580149

First Posted

October 15, 2015

Last Updated

September 19, 2016

Sponsor

Michael Wolzt, Prof. MD

1. Study Identification

Unique Protocol Identification Number

NCT02580149

Brief Title

The Effect of Ticagrelor or Clopidogrel on Endothelial Function During Acute and Chronic Treatment

Official Title

The Effect of an Acute Dose of Ticagrelor or Clopidogrel and of Treatment for 14 Days on Ischemia-reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

October 2015 (undefined)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Michael Wolzt, Prof. MD

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To investigate if treatment with ticagrelor can mitigate the transient loss of endothelium-dependent vasodilatation of the resistance vasculature following a short period of ischemia, compared with clopidogrel at standard clinical doses. The effect of ticagrelor or clopidogrel will be studied after a loading dose and after a two weeks period of regular intake on FBF in response to the vasodilators acetylcholine or nitroglycerin before and 10 min after a 20 min forearm ischemia, respectively.

Detailed Description

Ischemia-reperfusion (IR) causes tissue injury. Preclinical animal data suggest that ticagrelor but not clopidogrel protects against IR injury due to inhibition of cellular adenosine uptake and NO-synthase stimulation. It is unclear if this action is part of the beneficial clinical effect of ticagrelor in patients with a history of acute coronary syndrome. The preventive action of ticagrelor on IR injury may also be of interest for the peripheral vasculature, where IR injury is known to result in endothelial dysfunction. This study aims to investigate if treatment with ticagrelor can mitigate the transient loss of endothelium-dependent vasodilatation of the resistance vasculature following a short period of ischemia, compared with clopidogrel at standard clinical doses. We will study the effect of ticagrelor or clopidogrel after a loading dose and after a two weeks period of regular intake on forearm blood flow (FBF) reactivity in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (GTN; endothelium-independent vasodilator) before and 10 min after a 20 min forearm ischemia, respectively

6. Conditions and Keywords

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

Ischemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor

Arm Type

Active Comparator

Arm Description

Loading dose of 180 mg on day one, followed by a regular intake (90 mg twice daily) for 14 days

Arm Title

Clopidogrel

Arm Type

Active Comparator

Arm Description

Loading dose of 600 mg on day one, followed by a regular intake (75 mg once daily) for 14 days

Intervention Type

Drug

Intervention Name(s)

Ticagrelor

Other Intervention Name(s)

Brilique

Intervention Description

Subjects will receive an oral loading dose of 180 mg ticagrelor on study day 1 followed by a maintenance dose of 90 mg twice daily for 14 days (until study day 15).

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Other Intervention Name(s)

Plavix

Intervention Description

Subjects will receive a loading dose of 600 mg clopidogrel on the first study day followed by a maintenance dose of 75 mg once daily for 14 days

Primary Outcome Measure Information:

Title

Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholin (ACh) induced vasodilatation

Description

To test the effect of ticagrelor or clopidogrel on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia.

Time Frame

Change of the AUC before and 10 min after forearm ischemia

Secondary Outcome Measure Information:

Title

Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceroltrinitrate (GTN) induced vasodilatation

Description

To test the effect of ticagrelor or clopidogrel on GTN-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia.

Time Frame

Change of AUC before and 10 min after forearm ischemia

Title

(Expected) Peak plasma concentration of ticagrelor or clopidogrel

Time Frame

2.5 h after IMP intake

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male subjects; 18 - 40 years of age Body mass index between 18 and 27 kg/m2 Written informed consent Normal findings in medical & bleeding history Non-smoking Exclusion Criteria: Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease) Known disorders with increased bleeding risk (e.g. peridontosis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer) Known sensitivity to common causes of bleeding (e.g. nasal) History of thromboembolism History of occlusive vascular diseases History of vascular anomalies Impaired liver function (AST, ALT, gGT, bilirubin >2 x ULN) Impaired renal function (serum creatinine > 1.3 mg/dl) Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis HIV-1/2-Ab, HbsAg or HCV-Ab positive serology Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg Known allergy against any test agent under study Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol Participation in another clinical trial during the preceding 3 weeks

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Wolzt, Prof. MD

Organizational Affiliation

Department of Clinical Pharmacology, Medical University of Vienna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Vienna, Department of Clinical Pharmacology

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Learn more about this trial

The Effect of Ticagrelor or Clopidogrel on Endothelial Function During Acute and Chronic Treatment

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