Determinants of Oral Anticoagulants' Activity (ANTIGOAG)

Clinical, Biological and Genetic Determinants of Oral Anticoagulants' Activity

The primary objective of the present study is to determine the clinical, biological and genetic determinants of the anticoagulant activity in patients treated with either anti-IIa or anti Xa oral anticoagulants.

The secondary objective is to determine the clinical, biological or genetic determinants of hemorrhagic or thrombotic complications during a one year follow-up.

Results will lead to a better prediction of both drug response and risk of complications.

Study Overview

• Status: Terminated
• Conditions: Anticoagulant
• Intervention / Treatment: Genetic: PK-PD genetic polymorphisms

Detailed Description

Direct oral anticoagulants are changing clinical practices but a better knowledge of factors that may predict both drug response and risk of complications is need.

Anticoagulant activity is influenced by different factors. Because the biological activity is not easy to measure everywhere, it is important to clearly determine factors that are involved.

A cohort of 550 patients that receive either an anti-IIa or an anti-Xa will be recruited.

The primary objective is to determine clinical, biological and genetic determinants of anticoagulant activity.

This objective will be assessed through a multivariate logistic regression (separately for anti-IIa and anti-Xa) with anticoagulant activity as dependent variable.

Variables that will be included in the statistical model are those known or measured at the entry in the cohort such as :

• Clinical factors : age, sex, weight, dosage and time of the last dose
• Biological factors : serum creatinine level, plasma concentration of the drug
• Genetic polymorphisms :

Factor II and CES1 for anti-IIa drugs Factor X, CYP3, CYP3A4, CYP3A5 and ABCG2 for anti-Xa drugs.

By using the same statistical approach and the same variables, predictive factors of either hemorrhagic or thrombotic events will also be evaluated on the whole cohort. The occurence of hemorrhagic and thrombotic complications will then be assessed through a phone call every 3 months during a one-year follow-up.

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will be composed by all patient receiving a direct oral anticoagulant inside the University Hospital whatever the clinical indication

Description

Inclusion Criteria:

• Patient receiving direct oral anticoagulant
• Complete blood count and measure of hemostasis planned
• Patient able to give consent
• Patient with health insurance

Exclusion Criteria:

• Patient not able to consent
• Patient under 18 years old
• Patient refusal
• Patient without health insurance

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anti-IIa users; Determination of predictors of anticoagulant activity in a prospective cohort of patients using oral anti IIa anticoagulant including analysis of PK-PD genetic polymorphisms	Genetic: PK-PD genetic polymorphisms; PK-PD genetic polymorphisms analysis in patients receiving either anti-IIa or anti-Xa treatment
Anti-Xa users; Determination of predictors of anticoagulant activity in a prospective cohort of patients using oral anti Xa anticoagulant including analysis of PK-PD genetic polymorphisms	Genetic: PK-PD genetic polymorphisms; PK-PD genetic polymorphisms analysis in patients receiving either anti-IIa or anti-Xa treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of anticoagulant activity level	Multivariate analysis to determine clinical, biological or genetic predictors of anticoagulant activity level as measured by anti-IIa or anti-Xa activity	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of any hemorrhagic complication	Multivariate analysis to determine clinical, biological or genetic predictors of hemorrhagic complications under direct oral anticoagulant	One year follow-up
Occurence of any thrombotic complication	Multivariate analysis to determine clinical, biological or genetic predictors of thrombotic complications under direct oral anticoagulant	One year follow-up

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): October 15, 2019
• Study Completion (Actual): October 15, 2019

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: May 29, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: genetic polymorphisms; direct oral anticoagulant; hemorrhagic complication; thrombotic complication
• Other Study ID Numbers: 2014_26; 2015-A01596-43 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No