Pharmacogenetic Dosage Algorithm for Acenocoumarol

Study Overview
=================
Brief Summary
-----------------
The use of coumarins has been a challenge for doctors because of its narrow therapeutic range and they show great inter and intra-individual variability in the dose necessary to achieve an international normalized ratio (INR) within the therapeutic range. Among the factors influencing the interindividual variability in the dose required include age, weight, Vitamin K in the diet, comorbidity as well as drug interactions and in recent years has also seen the importance of pharmacogenetic factors.

Detailed Description
-----------------
Demographic and clinical factors contribute approximately 20% to the total variability of dose requirements. In recent years it has highlighted the close relationship between the dose requirements of coumarin drugs and certain polymorphisms of genes involved in pharmacokinetics and pharmacodynamics of these drugs. The use of dosing algorithms that include pharmacogenetic information may help in the dose selection, improving efficacy and reducing adverse events. Studies have shown the relationship between genotype variants of CYP2C9 and VKORC1, CYP4F2 and apolipoprotein E (ApoE), which together with the demographic and clinical variants can explain between 50-60% of the variability in the response to these drugs.

Official Title
-----------------
Creation and Validation of a Pharmacogenetic Dosage Algorithm for Acenocoumarol in Patients With Venous Thromboembolic Disease, Atrial Fibrillation and/or Mechanical Valvular Heart Prosthesis

Conditions
-----------------
Atrial Fibrillation, Venous Thromboses, Cardiac Valve Disease

Intervention / Treatment
-----------------
* Genetic: Acenocoumarol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with Auricular fibrillation, venous thromboembolic disease and cardiac valve replacement receiving acenocoumarol. Patients with stable dose of acenocoumarol (weekly dose variation of <20% in the last 3 months). Patients with an international normalised ratio within the range of 2 to 3 (in Auricular Fibrillation and venous thromboembolic disease) or 2.5 to 3.5 (in cardiac valve replacement) for at least the 3 previous consecutive months. Exclusion Criteria: Patients with renal failure (calculated creatinine clearance ≤30 ml/min), hepatic disease (stage C of Child Plough Stage), thyroid dysfunction and/or cancer.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Stable treatment with acenocoumarol<br>Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement. | Genetic: Acenocoumarol<br>* A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Creation of a pharmacogenetic algorithm of dosage for acenocoumarol |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validation of the pharmacogenetic algorithm. |  | Up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acenocoumarol, Cytochrome P450, Pharmacogenetics, Algorithm, CYP2C9, VKORC1, CYP4F2, P450 oxidoreductase (POR)