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
Condition: Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome
Study type: Interventional
Phase: Phase 2

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.
    


Intervention name(s): Clopidogrel; Ticagrelor; ASA; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1x Loading dose 600 mg 6x maintenance dose 150 mg; 1x Loading dose: 180 mg 6x Maintenance dose: 90 mg bid; 7x 100mg acetylsalicylic acid (clopidogrel arm)
1x 300 mg acetylsalicylic acid (ticagrelor arm); 7x 300mg acetylsalicylic acid placebo
Intervention MeSH terms: Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: ACS, Acute coronary syndrome