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

NCT ID: NCT02580149

Last Updated: 2016-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-07-31

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

Conditions

Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor

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

Group Type: ACTIVE_COMPARATOR

Ticagrelor

Intervention Type: DRUG

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).

Clopidogrel

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

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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

Interventions

Ticagrelor

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

Clopidogrel

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

Intervention Type: DRUG

Other Intervention Names

Brilique; Plavix

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Michael Wolzt, Prof. MD

OTHER

Sponsor Role: lead

Responsible Party

Michael Wolzt, Prof. MD

Prof. MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Wolzt, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Pharmacology, Medical University of Vienna

Locations

Medical University of Vienna, Department of Clinical Pharmacology

Vienna, Vienna, Austria

Countries

Austria

Other Identifiers

FBF-Tica-Clopi

Identifier Type: -

Identifier Source: org_study_id