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Pharmacogenetic Dosage Algorithm for Acenocoumarol

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ClinicalTrials.gov Identifier: NCT03015025
Recruitment Status : Completed
First Posted : January 9, 2017
Last Update Posted : January 9, 2017
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Atrial Fibrillation Venous Thromboses Cardiac Valve Disease Genetic: Acenocoumarol

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.

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Study Type : Observational
Actual Enrollment : 340 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Study Start Date : October 2011
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Stable treatment with acenocoumarol
Patients in stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement.
Genetic: Acenocoumarol
A blood sample was collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variants of POR genotypes.




Primary Outcome Measures :
  1. Creation of a pharmacogenetic algorithm of dosage for acenocoumarol [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Validation of the pharmacogenetic algorithm. [ Time Frame: Up to 5 years ]

Biospecimen Retention:   Samples With DNA
Patients' consent was requested for the preservation of their DNA sample, in case of new genes related to the pharmacokinetics or pharmacodynamics of acenocoumarol are discovered in the future.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients receiving stable anticoagulant treatment with acenocoumarol for auricular fibrillation, venous thromboembolic disease and/or cardiac valve replacement in Hospital La Paz and Barrio del Pilar primary care center.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03015025


Locations
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Spain
Hospital Universitario La Paz
Madrid, Spain, 28046
Sponsors and Collaborators
Instituto de Investigación Hospital Universitario La Paz
Investigators
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Principal Investigator: Antonio Carcas, MD, PhD Hospital Universitario La Paz

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Responsible Party: Instituto de Investigación Hospital Universitario La Paz
ClinicalTrials.gov Identifier: NCT03015025     History of Changes
Other Study ID Numbers: FC/HULP_005/2011
First Posted: January 9, 2017    Key Record Dates
Last Update Posted: January 9, 2017
Last Verified: September 2011
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Instituto de Investigación Hospital Universitario La Paz:
Acenocoumarol
Cytochrome P450
Pharmacogenetics
Algorithm
CYP2C9
VKORC1
CYP4F2
P450 oxidoreductase (POR)
Additional relevant MeSH terms:
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Atrial Fibrillation
Thrombosis
Venous Thrombosis
Heart Valve Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Acenocoumarol
Anticoagulants