Ignite Creation Date:
2024-05-06 @ 9:59 AM
Last Modification Date:
2024-10-26 @ 12:23 PM
Study NCT ID:
NCT03136510
Status:
TERMINATED
Last Update Posted:
2017-05-05
First Post:
2017-04-24
Brief Title:
Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban
Sponsor:
Hopital Lariboisière
Organization:
Hopital Lariboisière
Study Overview
Official Title:
Prospective Study With Biological Assessment Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban
Status:
TERMINATED
Status Verified Date:
2019-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
not enough patients
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ECAN
Brief Summary:
Apixaban is a potent oral selective reversible direct inhibitor of factor Xa with a favorable efficacy and safety profile in the prevention of non valvular NV atrial fibrillation AF It has been shown including by our group that D-dimers levels molecular marker of coagulation activity are predictive of the events including mortality in patient with AF independently of the antithrombotic treatment The aim of the study is to evaluate the changes in plasma levels of biomarkers of coagulation activation D-dimers prothrombin fragments F12 von Willebrand factor vWF and thrombin-antithrombin complexes TAT in response to apixaban treatment in patients with NVAF
Detailed Description:
This study is a prospective monocentric study with biological analyses The investigational product will be administered according to French health agency The duration of the study for each patient will be 3 months with 3 visits and from 3 to a maximum of 18 months for the clinical follow-up
Hypothesis Apixaban significantly decreases D-dimers and other markers of coagulation activation in patients with NVAF paroxysmic and chronic atrial fibrillation
Primary endpoint
Measurement of D-dimers at baseline before apixaban treatment and under chronic apixaban treatment at 3 months in the overall population
Secondary endpoints
Difference of the D-dimers levels between enrollment V1 and the final visit V3 at three months in both subgroups separately In the subgroup Bcomparison of D-dimers in patients previously treated by VKA V1 and under apixaban V3
Similarly than for D-dimers levels each following parameters will be analyzed for the overall population and for both subgroups separately
Difference of prothrombin fragments F1F2 levels between V1 and V3
Difference of thrombin and antithrombin complexes levels between V1 and V3
Difference of vWF levels between V1 and V3
Correlation will be evaluated between
AntiXa apixaban activity at trough and D-dimers difference
D-dimers difference and clinical follow-up ischemic events and-bleeding events V2 and V3 levels of each parameter will be compared to assess the delay of appearance of the apixaban effect if any Inflammation parameters C reactive protein and fibrinogen will be used as explicative for the other parameters
Effect on APTT activated partial thromboplastin time and PTprothrombin time will be compared to specific apixaban anti Xa activity
Subgroup analysis
Subgroups A and B newly diagnosed and VKA naïve NVAF and chronic NVAF
age 80 years
creatinine clearance 50 mlmin
gender Multivariate analysis for the primary endpoint
Statistical analysis Continuous variables will be analyzed for a normal distribution with the DAgostino-Pearson test They will be presented as mean and standard deviation SD and compared with Students unpaired t-test if normally distributed or presented as median and interquartile range and compared with Mann-Whitney rank-sum test if not Categorical variables will be presented as counts and percentages and will be compared by means of the χ2-test or Fishers exact test
Correlations between quantitative variables will be assessed with Pearson correlation coefficients Predictive factors will be determined using a stepwise multivariable logistic regression analysis In this study we will expect an initial D-dimers level around 1500ngml with a standard deviation of 700ngml in patients with newly diagnosed NVAF At 3 month we expect a level of D-dimers of 1000600ngml reduction of 500ngml compared to the enrolment visit A sample size of 60 patients has been estimated in this pilot study The study will include 60 patients with NVAF with 50 of patients with newly diagnosed NVAF Subgroup A n30 and the other 50 with NVAF previously treated by VKA Subgroup B n30
All information required by the protocol must be provided in the case report form The data will be transferred in the case report forms as and when they are obtained whether clinical or biological The investigators will make the data available strictly necessary for qua lity control and audit relating to the biomedical research in accordance with the legislative and regulatory provisions in force Articles L1121-3 and R5121-13 of the French Public Health Code
Those responsible for biomedical research quality control Article L1121-3 of the French Public Health Code will take all necessary precautions to ensure the confidentiality of information about the experimental medications the research the research subjects and in particular the identity of the subjects and the results obtained These individuals as well as the investigators themselves are subject to professional secrecy in accordance with the conditions set out in Articles 226-13 and 226-14 of the Penal Code
All Serious Adverse Events SAEs that occur following the subjects written consent to participate in the study through 30 days of discontinuation of dosing must be reported to Bristol-Myers Squibb Worldwide Safety and to the sponsor
Hypothesis Apixaban significantly decreases D-dimers and other markers of coagulation activation in patients with NVAF paroxysmic and chronic atrial fibrillation
Primary endpoint
Measurement of D-dimers at baseline before apixaban treatment and under chronic apixaban treatment at 3 months in the overall population
Secondary endpoints
Difference of the D-dimers levels between enrollment V1 and the final visit V3 at three months in both subgroups separately In the subgroup Bcomparison of D-dimers in patients previously treated by VKA V1 and under apixaban V3
Similarly than for D-dimers levels each following parameters will be analyzed for the overall population and for both subgroups separately
Difference of prothrombin fragments F1F2 levels between V1 and V3
Difference of thrombin and antithrombin complexes levels between V1 and V3
Difference of vWF levels between V1 and V3
Correlation will be evaluated between
AntiXa apixaban activity at trough and D-dimers difference
D-dimers difference and clinical follow-up ischemic events and-bleeding events V2 and V3 levels of each parameter will be compared to assess the delay of appearance of the apixaban effect if any Inflammation parameters C reactive protein and fibrinogen will be used as explicative for the other parameters
Effect on APTT activated partial thromboplastin time and PTprothrombin time will be compared to specific apixaban anti Xa activity
Subgroup analysis
Subgroups A and B newly diagnosed and VKA naïve NVAF and chronic NVAF
age 80 years
creatinine clearance 50 mlmin
gender Multivariate analysis for the primary endpoint
Statistical analysis Continuous variables will be analyzed for a normal distribution with the DAgostino-Pearson test They will be presented as mean and standard deviation SD and compared with Students unpaired t-test if normally distributed or presented as median and interquartile range and compared with Mann-Whitney rank-sum test if not Categorical variables will be presented as counts and percentages and will be compared by means of the χ2-test or Fishers exact test
Correlations between quantitative variables will be assessed with Pearson correlation coefficients Predictive factors will be determined using a stepwise multivariable logistic regression analysis In this study we will expect an initial D-dimers level around 1500ngml with a standard deviation of 700ngml in patients with newly diagnosed NVAF At 3 month we expect a level of D-dimers of 1000600ngml reduction of 500ngml compared to the enrolment visit A sample size of 60 patients has been estimated in this pilot study The study will include 60 patients with NVAF with 50 of patients with newly diagnosed NVAF Subgroup A n30 and the other 50 with NVAF previously treated by VKA Subgroup B n30
All information required by the protocol must be provided in the case report form The data will be transferred in the case report forms as and when they are obtained whether clinical or biological The investigators will make the data available strictly necessary for qua lity control and audit relating to the biomedical research in accordance with the legislative and regulatory provisions in force Articles L1121-3 and R5121-13 of the French Public Health Code
Those responsible for biomedical research quality control Article L1121-3 of the French Public Health Code will take all necessary precautions to ensure the confidentiality of information about the experimental medications the research the research subjects and in particular the identity of the subjects and the results obtained These individuals as well as the investigators themselves are subject to professional secrecy in accordance with the conditions set out in Articles 226-13 and 226-14 of the Penal Code
All Serious Adverse Events SAEs that occur following the subjects written consent to participate in the study through 30 days of discontinuation of dosing must be reported to Bristol-Myers Squibb Worldwide Safety and to the sponsor
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None