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

Sponsor

Medical University of Vienna (Other)

Overall Status

Completed

CT.gov ID

NCT02120092

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Clopidogrel Drug: Ticagrelor Drug: ASA Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

89 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

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: Ticagrelor 1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid Drug: ASA 7x 100mg acetylsalicylic acid (clopidogrel arm) 1x 300 mg acetylsalicylic acid (ticagrelor arm)
Placebo Comparator: Ticagrelor + Placebo	Drug: Ticagrelor 1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid Drug: Placebo 7x 300mg acetylsalicylic acid placebo

Outcome Measures

Primary Outcome Measures

ß-Thromboglobulin in shed blood 2h after first study drug intake [2 hours after first study drug intake]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

young, healthy males

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of Vienna	Vienna		Austria	1090

Sponsors and Collaborators

Medical University of Vienna

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sabine Eichinger, Ao. Univ. Prof. Sabine Eichinger, MD, Medical University of Vienna

ClinicalTrials.gov Identifier:

NCT02120092

Other Study ID Numbers:

ClopidogrelTicagrelorASA

First Posted:

Apr 22, 2014

Last Update Posted:

Apr 22, 2014

Last Verified:

Apr 1, 2014

Keywords provided by Sabine Eichinger, Ao. Univ. Prof. Sabine Eichinger, MD, Medical University of Vienna

ACS, Acute coronary syndrome

Additional relevant MeSH terms:

Acute Coronary Syndrome

Clopidogrel

Ticagrelor

Study Results

No Results Posted as of Apr 22, 2014