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

Ischemia Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580149
• Other study ID #: FBF-Tica-Clopi
• Status: Completed
• Phase: Phase 4
• First received: October 15, 2015
• Last updated: September 19, 2016
• Start date: October 2015
• Est. completion date: July 2016

Study information

• Verified date: September 2016
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia

Intervention

Drug:
• 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).
• 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

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Clinical Pharmacology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Michael Wolzt, Prof. MD

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Change of the AUC before and 10 min after forearm ischemia	No
Secondary	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.	Change of AUC before and 10 min after forearm ischemia	No
Secondary	(Expected) Peak plasma concentration of ticagrelor or clopidogrel		2.5 h after IMP intake	No