Pharmacogenetic Dosage Algorithm for Acenocoumarol

Completed

• Conditions: Atrial Fibrillation; Venous Thromboses; Cardiac Valve Disease
• Interventions: Genetic: Acenocoumarol

• Registration Number: NCT03015025
• Lead Sponsor: Instituto de Investigación Hospital Universitario La Paz

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.

Study Timeline

• Status Verified: 2011-09
• Study Start: 2011-10
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Study First Submitted: 2017-01-02
• Study First Submitted QC: 2017-01-05
• Last Update Submitted: 2017-01-05
• Study First Posted: 2017-01-09
• Last Update Posted: 2017-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 340

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Stable treatment with acenocoumarol	Acenocoumarol	Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement.

Primary Outcome Measures

Name	Time	Method
Creation of a pharmacogenetic algorithm of dosage for acenocoumarol	Up to 5 years

Secondary Outcome Measures

Name	Time	Method
Validation of the pharmacogenetic algorithm.	Up to 5 years

Trial Locations

Locations (1)

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain