The Effect of Clopidogrel and Ticagrelor With and Without Acetylsalicylic Acid (ASA) on Hemostatic System Activation at the Site of Plug Formation in Vivo in Man

Background: Coronary heart disease is the most common cause of death in industrialized countries. Revascularisation by percutaneous coronary angioplasty or thrombolysis is the main principle for treatment of the acute coronary syndrome. To inhibit platelet activity patients are routinely given acetylsalicylic acid (ASA) and clopidogrel, a second-generation thienopyridine. Recently, ticagrelor, a novel cyclopentyl-triazolo-pyrimidine with several pharmacological advantages, has demonstrated greater efficacy but a higher bleeding risk than clopidogrel. Coronary thrombus formation is a complex process and the antithrombotic mechanisms of platelet function inhibitors are incompletely understood. Studies in venous blood or in vitro do not truly reflect the in vivo circumstances as they often do not take into account flow conditions or the interaction between endothelium, blood cells and coagulation factors. Results from animal models may not be relevant for the prothrombotic mechanisms in humans. We have developed a technique that allows investigating hemostatic system activation directly at the site of thrombus formation in vivo in humans.

Aim: to compare the inhibitory effects of clopidogrel and ticagrelor (with and without concomitant ASA) on hemostatic system activation under circumstances close to the in vivo situation.

Design, patients and interventions: prospective, randomized, double-blind, placebo controlled parallel-group study with a 2x2 factorial design including 112 healthy volunteers who will be randomised to 4 treatment arms: ticagrelor or clopidogrel + placebo, ticagrelor or clopidogrel + ASA.

Outcome variables: Indicators of platelet and coagulation activation [ß-thromboglobulin and thromboxane B2 as well as prothrombin fragment F1+2 and D-Dimer, respectively] will be measured before and at several time points during a 8 day period in venous blood and in blood emerging from a standardized injury of the microvasculature to determine bleeding time (shed blood).

Statistical considerations: Sample size calculation is based on the percent change in the main outcome variable "β-TG in shed blood" from baseline to 2 hours after treatment start. Statistical analysis is based on the full analysis set, including all randomized subjects who received at least the starting dose of the study medication and for whom blood collections at baseline and at 2 hours after treatment start have been performed.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Clopidogrel; Drug: ASA; Drug: Placebo; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• young, healthy males

Exclusion Criteria:

• history of bleeding
• any medication
• known intolerance to study drug(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel + ASA	Drug: Clopidogrel; 1x Loading dose 600 mg 6x maintenance dose 150 mg; Drug: ASA; 7x 100mg acetylsalicylic acid (clopidogrel arm) 1x 300 mg acetylsalicylic acid (ticagrelor arm)
Placebo Comparator: Clopidogrel + Placebo	Drug: Clopidogrel; 1x Loading dose 600 mg 6x maintenance dose 150 mg; Drug: Placebo; 7x 300mg acetylsalicylic acid placebo
Active Comparator: Ticagrelor + ASA	Drug: ASA; 7x 100mg acetylsalicylic acid (clopidogrel arm) 1x 300 mg acetylsalicylic acid (ticagrelor arm); Drug: Ticagrelor; 1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid
Placebo Comparator: Ticagrelor + Placebo	Drug: Placebo; 7x 300mg acetylsalicylic acid placebo; Drug: Ticagrelor; 1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ß-Thromboglobulin in shed blood 2h after first study drug intake	2 hours after first study drug intake

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Sabine Eichinger-Hasenauer, MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 17, 2014
• First Submitted That Met QC Criteria: April 17, 2014
• First Posted (Estimate): April 22, 2014

Study Record Updates

• Last Update Posted (Estimate): April 22, 2014
• Last Update Submitted That Met QC Criteria: April 17, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: ACS, Acute coronary syndrome
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: ClopidogrelTicagrelorASA