Ignite Creation Date:
2024-05-06 @ 2:36 AM
Last Modification Date:
2024-10-26 @ 11:20 AM
Study NCT ID:
NCT02080858
Status:
COMPLETED
Last Update Posted:
2015-04-07
First Post:
2014-03-05
Brief Title:
Triple vs Dual Therapy
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
The Effect of Ticagrelor and Apixaban With or Without Acetylsalicylic Acid on Markers of Coagulation Activation at the Site of Thrombus Formation in Vivo in Healthy Male Subjects and in an ex Vivo Perfusion Chamber Model at High and Low Shear Rate
Status:
COMPLETED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
The acute coronary syndrome ACS is a complication of coronary artery disease CAD and associated with increased mortality Dual antiplatelet therapy of acetylsalicylic acid ASA with P2Y12 receptor antagonists such as clopidogrel is a cornerstone in the treatment of patients with advanced CAD Due to delayed onset of action intersubject variability or resistance to clopidogrel different platelet aggregation inhibitors have been developed Ticagrelor is a reversible P2Y12 receptor antagonist with superior efficacy compared to clopidogrel in the prevention of cardiovascular death in these patients
Atrial fibrillation AF is also associated with thromboembolic events and substantial mortality Beside vitamin K antagonists VKA phenprocoumon for stroke prevention in patients with AF the direct factor Xa inhibitor apixaban has recently received approval for prophylactic treatment of patients with non-valvular AF
However there is a lack of efficacy or safety data for the combined impact of antithrombotic drugs in patients requiring arterial and venous thromboembolic prophylaxis due to their underlying co-morbidities One trial suggests treatment with VKA clopidogrel without ASA as equal effective as antithrombotic triple therapy with ASA in this population However the effect in combination with novel oral anticoagulants has not been investigated so far
Study objectives
To evaluate the effect of ticagrelor apixaban in combination with or without ASA at steady state on markers of coagulation activation and on thrombus size in an ex vivo perfusion chamber experiment Additionally plasma samples will be analysed for PK-data ticagrelor apixaban concentrations
Study design
A single-centre prospective sequential controlled analyst-blinded study in two groups Subjects will receive ticagrelor apixaban in combination with study A or without study B ASA All IMPs will be administered at doses indicated for stroke prevention in AF lower dose 25mg due to ethical concerns or ACS Markers on thrombin generation and platelet activation will be studied in venous blood where coagulation is in resting state and in shed blood where the clotting system is activated in the microvasculature in vivo prothrombin fragment 12 F12 thrombin-anti-thrombin TAT β-thromboglobulin β-TG Additionally inhibition of factor Xa activity and concentrations of ticagrelor and apixaban will be assessed in venous blood Further thrombus size of clots formed in an ex vivo perfusion chamber will be determined by measurement of D-Dimer and p-Selectin levels
Study population A total of 40 healthy non-smoking and drug-free male volunteers will be enrolled study A and B n 20 per group
Main outcome variables
β-TG in shed blood
Additional outcome variables
F12 and TAT in shed blood
fibrin formation D-Dimer and platelet deposition p-Selectin in an ex vivo perfusion chamber model of thrombosis
β-TG F12 TAT inhibition of factor Xa in venous blood
PT aPTT and ACT in venous blood
ticagrelor apixaban plasma concentrations
shed blood volume
The acute coronary syndrome ACS is a complication of coronary artery disease CAD and associated with increased mortality Dual antiplatelet therapy of acetylsalicylic acid ASA with P2Y12 receptor antagonists such as clopidogrel is a cornerstone in the treatment of patients with advanced CAD Due to delayed onset of action intersubject variability or resistance to clopidogrel different platelet aggregation inhibitors have been developed Ticagrelor is a reversible P2Y12 receptor antagonist with superior efficacy compared to clopidogrel in the prevention of cardiovascular death in these patients
Atrial fibrillation AF is also associated with thromboembolic events and substantial mortality Beside vitamin K antagonists VKA phenprocoumon for stroke prevention in patients with AF the direct factor Xa inhibitor apixaban has recently received approval for prophylactic treatment of patients with non-valvular AF
However there is a lack of efficacy or safety data for the combined impact of antithrombotic drugs in patients requiring arterial and venous thromboembolic prophylaxis due to their underlying co-morbidities One trial suggests treatment with VKA clopidogrel without ASA as equal effective as antithrombotic triple therapy with ASA in this population However the effect in combination with novel oral anticoagulants has not been investigated so far
Study objectives
To evaluate the effect of ticagrelor apixaban in combination with or without ASA at steady state on markers of coagulation activation and on thrombus size in an ex vivo perfusion chamber experiment Additionally plasma samples will be analysed for PK-data ticagrelor apixaban concentrations
Study design
A single-centre prospective sequential controlled analyst-blinded study in two groups Subjects will receive ticagrelor apixaban in combination with study A or without study B ASA All IMPs will be administered at doses indicated for stroke prevention in AF lower dose 25mg due to ethical concerns or ACS Markers on thrombin generation and platelet activation will be studied in venous blood where coagulation is in resting state and in shed blood where the clotting system is activated in the microvasculature in vivo prothrombin fragment 12 F12 thrombin-anti-thrombin TAT β-thromboglobulin β-TG Additionally inhibition of factor Xa activity and concentrations of ticagrelor and apixaban will be assessed in venous blood Further thrombus size of clots formed in an ex vivo perfusion chamber will be determined by measurement of D-Dimer and p-Selectin levels
Study population A total of 40 healthy non-smoking and drug-free male volunteers will be enrolled study A and B n 20 per group
Main outcome variables
β-TG in shed blood
Additional outcome variables
F12 and TAT in shed blood
fibrin formation D-Dimer and platelet deposition p-Selectin in an ex vivo perfusion chamber model of thrombosis
β-TG F12 TAT inhibition of factor Xa in venous blood
PT aPTT and ACT in venous blood
ticagrelor apixaban plasma concentrations
shed blood volume
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None