Ignite Creation Date:
2024-05-06 @ 1:27 AM
Last Modification Date:
2024-10-26 @ 11:04 AM
Study NCT ID:
NCT01812200
Status:
COMPLETED
Last Update Posted:
2014-03-06
First Post:
2013-03-09
Brief Title:
Antithrombotic Triple Therapy in Humans
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
A Prospective Randomized Controlled Analyst-blinded Parallel Group Study to Investigate the Effect of Antithrombotic Triple Therapy With Ticagrelor and Acetylsalicylic Acid in Combination With Dabigatran or Rivaroxaban or Phenprocoumon on Markers of Coagulation Activation in Venous and Shed Blood in Healthy Male Subjects
Status:
COMPLETED
Status Verified Date:
2014-03
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:
BackgroundThe 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 rivaroxaban and the direct thrombin inhibitor dabigatran have 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
Study objectives To evaluate the effect of ticagrelor ASA in combination with dabigatran rivaroxaban or phenprocoumon at steady state on markers of coagulation activation The effects on coagulation activation will also be studied after a single dose of dabigatran rivaroxaban or ticagrelor and at a therapeutic INR of phenprocoumon
Study design A single-centre prospective randomized controlled analyst-blinded study in three parallel-groups Subjects will receive ticagrelor ASA in combination with dabigatran treatment A rivaroxaban treatment B or phenprocoumon treatment C All IMPs will be administered at doses indicated for stroke prevention in AF 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 D-Dimer thromboxane B2 TxB2 CD40 ligand CD40L p-Selectin Further the endogenous thrombin potential ETP inhibition of factor Xa activity activated partial thromboplastin time aPTT prothrombin time PT Biophen and Hemoclot will be assessed in venous blood
Study population A total of 60 healthy non-smoking and drug-free male volunteers will be enrolled in this trial and randomized into one of three balanced groups treatment A B and C n 20 per group
Main outcome variables β-TG F12 and TAT in shed blood
Additional outcome variables
D-Dimer TxB2 CD40L and p-Selectin in shed blood
β-TG F12 TAT D-Dimer TxB2 CD40L p-Selectin ETP aPTT PT inhibition of factor Xa Biophen and Hemoclot in venous blood
Risk benefit assessmentTotal blood loss will be dependent on treatment allocation between 330 ml and 510 ml throughout the entire study period of 4 - 5 weeks This amount of venous blood is considered to be acceptable in this healthy population Blood sampling procedures may cause mild and transient pain A minor haematoma may occur at the site of needle insertions Bleeding time incisions may leave small persistent scars Administration of the study drugs in particular as triple combination for 5 days results in transient hypocoagulability and may cause overt or occult bleeding The risk is considered low in the healthy subjects under study Continuous monitoring of safety parameters haemoglobin haematocrit platelet count coagulation and surveillance of the overall status will be performed during study participation Subjects will be instructed to avoid vigorous physical exercise and handling of hazardous machinery during study participation ASA dabigatran and rivaroxaban can cause gastrointestinal discomfort Other side effects are rare
The combination of these novel anticoagulants dabigatran rivaroxaban ticagrelor has not been investigated so far Conducting this study in a healthy population limits potential bleeding risk reported from drug interactions and impaired liver or renal function which may influence the pharmacokinetics and -dynamics of the investigational products
This study can provide information on haemostatic system activation in vivo during triple treatment with antithrombotic drugs which is indicated for patients with AF and ACS The results of this study may provide dosing guidance for risk reduction of patients with ACS and AF
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 rivaroxaban and the direct thrombin inhibitor dabigatran have 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
Study objectives To evaluate the effect of ticagrelor ASA in combination with dabigatran rivaroxaban or phenprocoumon at steady state on markers of coagulation activation The effects on coagulation activation will also be studied after a single dose of dabigatran rivaroxaban or ticagrelor and at a therapeutic INR of phenprocoumon
Study design A single-centre prospective randomized controlled analyst-blinded study in three parallel-groups Subjects will receive ticagrelor ASA in combination with dabigatran treatment A rivaroxaban treatment B or phenprocoumon treatment C All IMPs will be administered at doses indicated for stroke prevention in AF 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 D-Dimer thromboxane B2 TxB2 CD40 ligand CD40L p-Selectin Further the endogenous thrombin potential ETP inhibition of factor Xa activity activated partial thromboplastin time aPTT prothrombin time PT Biophen and Hemoclot will be assessed in venous blood
Study population A total of 60 healthy non-smoking and drug-free male volunteers will be enrolled in this trial and randomized into one of three balanced groups treatment A B and C n 20 per group
Main outcome variables β-TG F12 and TAT in shed blood
Additional outcome variables
D-Dimer TxB2 CD40L and p-Selectin in shed blood
β-TG F12 TAT D-Dimer TxB2 CD40L p-Selectin ETP aPTT PT inhibition of factor Xa Biophen and Hemoclot in venous blood
Risk benefit assessmentTotal blood loss will be dependent on treatment allocation between 330 ml and 510 ml throughout the entire study period of 4 - 5 weeks This amount of venous blood is considered to be acceptable in this healthy population Blood sampling procedures may cause mild and transient pain A minor haematoma may occur at the site of needle insertions Bleeding time incisions may leave small persistent scars Administration of the study drugs in particular as triple combination for 5 days results in transient hypocoagulability and may cause overt or occult bleeding The risk is considered low in the healthy subjects under study Continuous monitoring of safety parameters haemoglobin haematocrit platelet count coagulation and surveillance of the overall status will be performed during study participation Subjects will be instructed to avoid vigorous physical exercise and handling of hazardous machinery during study participation ASA dabigatran and rivaroxaban can cause gastrointestinal discomfort Other side effects are rare
The combination of these novel anticoagulants dabigatran rivaroxaban ticagrelor has not been investigated so far Conducting this study in a healthy population limits potential bleeding risk reported from drug interactions and impaired liver or renal function which may influence the pharmacokinetics and -dynamics of the investigational products
This study can provide information on haemostatic system activation in vivo during triple treatment with antithrombotic drugs which is indicated for patients with AF and ACS The results of this study may provide dosing guidance for risk reduction of patients with ACS and AF
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