Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban — ECAN  

Coagulation Disorder Clinical Trial

Official title: Prospective Study With Biological Assessment: Evolution of Coagulation Activity in Non Valvular Atrial Fibrillation Patients Under Apixaban

Status Recruiting

Clinical Trial 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 F1+2, von Willebrand factor (vWF) and thrombin-antithrombin complexes (TAT) in response to apixaban treatment in patients with NVAF.

Clinical Trial 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 B,comparison 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 F1+F2 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 PT(prothrombin 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 ml/min,

• gender Multivariate analysis for the primary endpoint

Statistical analysis Continuous variables will be analyzed for a normal distribution with the D'Agostino-Pearson test. They will be presented as mean and standard deviation (SD) and compared with Student's 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 Fisher's 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 1500ng/ml with a standard deviation of ±700ng/ml in patients with newly diagnosed NVAF. At 3 month, we expect a level of D-dimers of 1000±600ng/ml (reduction of 500ng/ml 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, n=30) and the other 50% with NVAF previously treated by VKA (Subgroup B, n=30).

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 L.1121-3 and R.5121-13 of the French Public Health Code).

Those responsible for biomedical research quality control (Article L.1121-3 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 subject's 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. ;

Related Conditions & MeSH terms

• Atrial Fibrillation
• Blood Coagulation Disorders
• Coagulation Disorder
• Hemostatic Disorders
• Non Valvular Atrial Fibrillation

• NCT number: NCT03136510
• Study type: Interventional
• Source: Hopital Lariboisière
• Contact: Claire Bal dit Sollier
• Phone: (33) 1 49 95 85 78
• Email: claire.bal@aphp.fr
• Status: Recruiting
• Phase: N/A
• Start date: September 2016
• Completion date: June 2018