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

NCT ID: NCT02120092

Last Updated: 2014-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-12-31

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.

Conditions

Acute Coronary Syndrome

Study Design

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

Study Groups

Clopidogrel + ASA

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

1x Loading dose 600 mg 6x maintenance dose 150 mg

ASA

Intervention Type: DRUG

7x 100mg acetylsalicylic acid (clopidogrel arm)

1x 300 mg acetylsalicylic acid (ticagrelor arm)

Clopidogrel + Placebo

Group Type: PLACEBO_COMPARATOR

Clopidogrel

Intervention Type: DRUG

1x Loading dose 600 mg 6x maintenance dose 150 mg

Placebo

Intervention Type: DRUG

7x 300mg acetylsalicylic acid placebo

Ticagrelor + ASA

Group Type: ACTIVE_COMPARATOR

Ticagrelor

Intervention Type: DRUG

1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid

ASA

Intervention Type: DRUG

7x 100mg acetylsalicylic acid (clopidogrel arm)

1x 300 mg acetylsalicylic acid (ticagrelor arm)

Ticagrelor + Placebo

Group Type: PLACEBO_COMPARATOR

Ticagrelor

Intervention Type: DRUG

1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid

Placebo

Intervention Type: DRUG

7x 300mg acetylsalicylic acid placebo

Interventions

Clopidogrel

1x Loading dose 600 mg 6x maintenance dose 150 mg

Intervention Type: DRUG

Ticagrelor

1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid

Intervention Type: DRUG

ASA

7x 100mg acetylsalicylic acid (clopidogrel arm)

1x 300 mg acetylsalicylic acid (ticagrelor arm)

Intervention Type: DRUG

Placebo

7x 300mg acetylsalicylic acid placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• young, healthy males

Exclusion Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Sabine Eichinger

Ao. Univ. Prof. Sabine Eichinger, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sabine Eichinger-Hasenauer, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

ClopidogrelTicagrelorASA

Identifier Type: -

Identifier Source: org_study_id