New Oral Direct Anticoagulants in Patients 80 Years Old and Over : a Population Pharmacokinetics Study

Study Overview
=================
Brief Summary
-----------------
Several new oral direct anticoagulants have been recently marketed. However, only a few, limited, studies have provided data about the pharmacology of new oral direct anticoagulants in older persons. This study try to better define wether the pharmacology of each of these 3 drugs (dabigatran, rivaroxaban and apixaban) is actually significantly different in very older patients (over 80) and to which extend. The investigators also try to characterize the main determinants (age, weight, renal function, co-morbidities, etc) of the variability observed between individuals in their response to he drugs studied. The method employed is a population pharmacokinetic/pharmacodynamic study.

Detailed Description
-----------------
Several new oral direct anticoagulants have been recently marketed. A main indication for taking these drugs is atrial fibrillation and, in everyday practice, most patients with atrial fibrillation are older people. However, only a few, limited, studies have provided data about the pharmacology of new oral direct anticoagulants in older persons. Furthermore, this limited data strongly suggests that, in older patients, mean concentrations, overall exposition and half-live of these drugs are increased, as compared with younger people. This study try to better define wether the pharmacology of each of these 3 drugs (dabigatran, rivaroxaban and apixaban) is actually significantly different in very older patients (over 80) and to which extend. The investigators also try to characterize the main determinants (age, weight, renal function, co-morbidities, etc) of the variability observed between individuals in their response to he drugs studied. The method employed is a population pharmacokinetic/pharmacodynamic study. This is, many people (projected 225 patients) will have a few blood samples each and all data will be pooled using statistical methods specific to this kind of studies. Each patient will have one to five blood samples, taken at te same time that routine blood analysis, to determine plasma concentrations of the studied drug. In addition, patients will be followed for thrombotic and haemorrhagic events at 6 and 12 months.

Official Title
-----------------
Study of Interindividual Variability in the Response to New Oral Direct Anticoagulants (Dabigatran Etexilate, Rivaroxaban or Apixaban) in Patients 80 Years Old and Over, Using a Population Pharmacokinetics Approach.

Conditions
-----------------
Atrial Fibrillation

Intervention / Treatment
-----------------
* Other: Plasma drug concentrations


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 80 years or older Under treatment with dabigatran, rivaroxaban or apixaban For non-valvular atrial fibrillation Exclusion Criteria: Mechanical (non-biological) heart valve Any severe condition leading to a short estimated life expectance (a few months)

Ages Eligible for Study
-----------------
Minimum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Main cohort (only cohort of the study)<br>Patients aged 80 years or older under treatment with dabigatran, rivaroxaban or apixaban because atrial fibrillation. All patients will have plasma drug concentrations measured and will be followed afterwards similarly | Other: Plasma drug concentrations<br>* Measure of plasma concentrations of the anticoagulant drug taken by the patient<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacologic parameters of new oral anticoagulants in elderly patients | Estimated area under the curve (AUC) of each of the 3 drugs studied | 1 to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic events | Any thromboembolic event (composite of ischemic stroke, systemic embolism or acute coronary syndrome) in the year after inclusion | 1 year | 
| Hemorrhagic events | Major hemorrhagic events in the year after inclusion | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anticoagulants, Factor Xa Inhibitors, Antithrombins, Pharmacokinetics, Aged, 80 years and older