Ignite Creation Date:
2024-05-05 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 9:53 AM
Study NCT ID:
NCT00725829
Status:
UNKNOWN
Last Update Posted:
2009-02-10
First Post:
2008-07-07
Brief Title:
Hypolipemic Treatment in Acute Coronary Syndrome ACS Antithrombotic Effects
Sponsor:
Jagiellonian University
Organization:
Jagiellonian University
Study Overview
Official Title:
Effects of Simvastatin Versus Simvastatin Combined With Ezetimibe on Blood Coagulation in Patients With Acute Coronary Events Relationship With Cholesterol-Lowering and Anti-Inflammatory Properties
Status:
UNKNOWN
Status Verified Date:
2009-02
Last Known Status:
RECRUITING
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:
The aim of the current study is to evaluate whether treatment with high doses of simvastatin can reduce coagulation activation in patients with acute coronary syndromes and if ezetimibe in conjunction with simvastatin may affect blood clotting in a similar manner
The investigators hypotheses are as follows
1 Intensive lipid lowering treatment with simvastatin 40 mgday and simvastatin 40 mgday combined with ezetimibe 10 mgday initiated after acute coronary syndrome leads to attenuation of blood coagulation including reduced thrombin generation thrombin-mediated coagulant reactions and improved structure of plasma clots
2 Anticoagulant effects of simvastatin are weaker than those observed during administration of simvastatin and ezetimibe
The investigators hypotheses are as follows
1 Intensive lipid lowering treatment with simvastatin 40 mgday and simvastatin 40 mgday combined with ezetimibe 10 mgday initiated after acute coronary syndrome leads to attenuation of blood coagulation including reduced thrombin generation thrombin-mediated coagulant reactions and improved structure of plasma clots
2 Anticoagulant effects of simvastatin are weaker than those observed during administration of simvastatin and ezetimibe
Detailed Description:
Clinical status will be evaluated during hospitalization and then on the out-patient basis All cardiovascular events fatal or nonfatal myocardial infarction unstable angina sudden cardiac death all-cause death stroke TIA will be recorded and the patients who underwent acute PCI will have a follow-up coronary angiography performed according to current recommendations However the clinical analysis is not a major gaol of this study
The investigators plan to evaluate following parameters
Whole blood morphology creatinine glucose sodium potassium urea lipid profile CK AST fibrinogen using standard methods in hospital laboratory
Inflammation markers - fibrinogen nephelometry Dade Behring high-sensitivity C-reactive protein nephelometry Dade Behring interleukin 6 ELISA RD Systems
Thrombin generation markers in peripheral blood - thrombin-antithrombin complexes TAT ELISA Dade Behring prothrombin fragments 12 F12 ELISA Dade Behring
Fibrin clot permeation and susceptibility to lysis - measurement of Darcys constant dimensions of pores in the structure of the clot by measurement of volume of buffer 005 moll Tris HCl with 015 moll NaCl penetrating through the fibrin gel made in polystyrene pipes 13 mm in diameter with 100 ul of citrate plasma and after addition of 1Uml human thrombin and 20 mmoll calcium chloride in room temperature within 120 minutes according to methodology described by Mills and al
Fibrin gel turbidimetry - plasma mixed with Tris buffer prepared as mentioned above in 23 ratio after addition 1 Uml thrombin and 16 mmoll calcium chloride will be analyzed in the UV spectrometer wave length 405 nm Following variables will be measured initiation time absorption increasing time and absorption value in plateau approximately 10 minutes after addition of thrombin to the mixture After 2 hours spectrophotometry assessment of the clot will be performed 400 to 800 nm to measure the pore size and thickness of fibrin fibers using the Carr equation modified by Wolberg Then fibrinolysis of fibrin gel will be measured by means of turbidimetry Another lysis assay based on the measurement of D-dimer levels in the effluent flowing through fibrin gels will be performed according to the method of Collet et al
Activation of the coagulation system in a minimally modified blood model according to Rand et al Non-anticoagulated blood will be divided into 10 1-ml samples added to the tubes with TF and phospholipids and then clotting will be stopped by an anticoagulant cocktail In the supernatant samples Western blotting and HPLC analysis of fibrinopeptides will be performed as described previously
In 40 patients allocated at a random we will assess activation of coagulation system using the vascular injury model according to a procedure developed by us
We will measure
Activation of prothrombin
Conversion of fibrinogen to fibrin
Activation of factor V and inactivation of factor Va
Activation of factor XIII
Activation of TAFI
Thrombin generation
Genetic analysis The investigators will determine the PlA1 PlA2 polymorphism in the integrin β3 gene using the PCR technique in DNA samples collected from peripheral blood leukocytes
Additionally we are going to search for polymorphism of promoter region of IL-6 G-174C also by means of PCR in DNA collected from peripheral blood leukocytes using prim-ers 5- AAT CTT TGT TGG AGG GTG AG and 5- ACA TGC CAA GTG CTG AGT CA and restriction endonuclease Sfa NI on 2 agarose gel
The investigators plan to evaluate following parameters
Whole blood morphology creatinine glucose sodium potassium urea lipid profile CK AST fibrinogen using standard methods in hospital laboratory
Inflammation markers - fibrinogen nephelometry Dade Behring high-sensitivity C-reactive protein nephelometry Dade Behring interleukin 6 ELISA RD Systems
Thrombin generation markers in peripheral blood - thrombin-antithrombin complexes TAT ELISA Dade Behring prothrombin fragments 12 F12 ELISA Dade Behring
Fibrin clot permeation and susceptibility to lysis - measurement of Darcys constant dimensions of pores in the structure of the clot by measurement of volume of buffer 005 moll Tris HCl with 015 moll NaCl penetrating through the fibrin gel made in polystyrene pipes 13 mm in diameter with 100 ul of citrate plasma and after addition of 1Uml human thrombin and 20 mmoll calcium chloride in room temperature within 120 minutes according to methodology described by Mills and al
Fibrin gel turbidimetry - plasma mixed with Tris buffer prepared as mentioned above in 23 ratio after addition 1 Uml thrombin and 16 mmoll calcium chloride will be analyzed in the UV spectrometer wave length 405 nm Following variables will be measured initiation time absorption increasing time and absorption value in plateau approximately 10 minutes after addition of thrombin to the mixture After 2 hours spectrophotometry assessment of the clot will be performed 400 to 800 nm to measure the pore size and thickness of fibrin fibers using the Carr equation modified by Wolberg Then fibrinolysis of fibrin gel will be measured by means of turbidimetry Another lysis assay based on the measurement of D-dimer levels in the effluent flowing through fibrin gels will be performed according to the method of Collet et al
Activation of the coagulation system in a minimally modified blood model according to Rand et al Non-anticoagulated blood will be divided into 10 1-ml samples added to the tubes with TF and phospholipids and then clotting will be stopped by an anticoagulant cocktail In the supernatant samples Western blotting and HPLC analysis of fibrinopeptides will be performed as described previously
In 40 patients allocated at a random we will assess activation of coagulation system using the vascular injury model according to a procedure developed by us
We will measure
Activation of prothrombin
Conversion of fibrinogen to fibrin
Activation of factor V and inactivation of factor Va
Activation of factor XIII
Activation of TAFI
Thrombin generation
Genetic analysis The investigators will determine the PlA1 PlA2 polymorphism in the integrin β3 gene using the PCR technique in DNA samples collected from peripheral blood leukocytes
Additionally we are going to search for polymorphism of promoter region of IL-6 G-174C also by means of PCR in DNA collected from peripheral blood leukocytes using prim-ers 5- AAT CTT TGT TGG AGG GTG AG and 5- ACA TGC CAA GTG CTG AGT CA and restriction endonuclease Sfa NI on 2 agarose gel
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