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

NCT02120092 | Completed Phase 2 DMC

• 1 other identifier: ClopidogrelTicagrelorASA
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

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

Keywords

ACS, Acute coronary syndrome

Outcome Measures

Primary Outcomes (1)

• ß-Thromboglobulin in shed blood 2h after first study drug intake

  2 hours after first study drug intake

Study Arms (4)

Clopidogrel + ASA

ACTIVE COMPARATOR

Drug: Clopidogrel; Drug: ASA

Clopidogrel + Placebo

PLACEBO COMPARATOR

Drug: Clopidogrel; Drug: Placebo

Ticagrelor + ASA

ACTIVE COMPARATOR

Drug: Ticagrelor; Drug: ASA

Ticagrelor + Placebo

PLACEBO COMPARATOR

Drug: Ticagrelor; Drug: Placebo

Interventions

Clopidogrel DRUG

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

Clopidogrel + ASA; Clopidogrel + Placebo

Ticagrelor DRUG

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

Ticagrelor + ASA; Ticagrelor + Placebo

ASA DRUG

7x 100mg acetylsalicylic acid (clopidogrel arm) 1x 300 mg acetylsalicylic acid (ticagrelor arm)

Clopidogrel + ASA; Ticagrelor + ASA

Placebo DRUG

7x 300mg acetylsalicylic acid placebo

Clopidogrel + Placebo; Ticagrelor + Placebo

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• young, healthy males

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Sabine Eichinger-Hasenauer, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ao. Univ. Prof. Sabine Eichinger, MD

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 22, 2014
• Study Start: October 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 22, 2014

Record last verified: 2014-04

Locations

AU (1)