Pharmacogenetic Dosage Algorithm for Acenocoumarol

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03015025
• Other study ID #: FC/HULP_005/2011
• Status: Completed
• Phase: N/A
• First received: January 2, 2017
• Last updated: January 5, 2017
• Start date: October 2011
• Est. completion date: October 2013

Study information

• Verified date: September 2011
• Source: Instituto de Investigación Hospital Universitario La Paz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación ClínicaSpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 340
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cardiac Valve Disease
• Heart Valve Diseases
• Thrombosis
• Venous Thromboses
• Venous Thrombosis

Intervention

Genetic:
• Acenocoumarol
A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.

Locations

Country	Name	City	State
Spain	Hospital Universitario La Paz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigación Hospital Universitario La Paz

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Creation of a pharmacogenetic algorithm of dosage for acenocoumarol		Up to 5 years	No
Secondary	Validation of the pharmacogenetic algorithm.		Up to 5 years	No