Determinants of Oral Anticoagulants' Activity

Terminated

• Conditions: Anticoagulant
• Interventions: Genetic: PK-PD genetic polymorphisms

• Registration Number: NCT03172546
• Lead Sponsor: University Hospital, Lille

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-05-24
• Study First Submitted QC: 2017-05-29
• Study First Posted: 2017-06-01
• Study Start: 2017-07-06
• Status Verified: 2019-10
• Primary Completion: 2019-10-15
• Study Completion: 2019-10-15
• Last Update Submitted: 2019-10-15
• Last Update Posted: 2019-10-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Anti-IIa users	PK-PD genetic polymorphisms	Determination of predictors of anticoagulant activity in a prospective cohort of patients using oral anti IIa anticoagulant including analysis of PK-PD genetic polymorphisms
Anti-Xa users	PK-PD genetic polymorphisms	Determination of predictors of anticoagulant activity in a prospective cohort of patients using oral anti Xa anticoagulant including analysis of PK-PD genetic polymorphisms

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Hospital; 🇫🇷 Lille, France