Ignite Creation Date:
2024-05-06 @ 2:42 AM
Last Modification Date:
2024-10-26 @ 11:22 AM
Study NCT ID:
NCT02103101
Status:
COMPLETED
Last Update Posted:
2018-07-18
First Post:
2014-03-31
Brief Title:
Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events
Sponsor:
Centre Hospitalier Universitaire de Besancon
Organization:
Centre Hospitalier Universitaire de Besancon
Study Overview
Official Title:
Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events
Status:
COMPLETED
Status Verified Date:
2018-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Pgp NACO
Brief Summary:
Vitamin K antagonists were hampered by several disadvantages such as the need for frequent monitoring In this context new oral anticoagulants NOACs have been developed and are now available on the market These NOACs like all anticoagulant drugs continue to be associated with an increased risk of bleeding In addition the lack of antidote and the absence of valid data regarding biological monitoring can pose problems in case of overdose or when emergency surgery is required Studies investigating the pharmacokinetic properties of rivaroxaban and dabigatran two NOACs now approved for the market have shown high variability between individuals with coefficients of variation of up to 60 for some pharmacokinetic parameters in patients treated after orthopaedic surgery The relation between plasma concentrations of NOAC and bleeding risk has been clearly established in clinical trials
Dabigtran rivaroxaban and apixaban are known substrates of P-glycoprotein Pgp Pgp activity can be affected by pharmacological inducing or inhibiting agents This can lead to a significant change in the pharmacokinetics of NOACs with a decrease or increase respectively in the level of intestinal absorption leading to respectively reduced or increased plasma concentrations of the drug Furthermore there exist genetic mutations of Pgp presenting in particular a lower level of activity than the non-mutated protein We hypothesized that the polymorphisms mutations of the ABCB1 gene that codes for Pgp could influence plasma concentrations of dabigatran rivaroxaban and apixaban and consequently impact on the concentration of NOACs and as a corollary on the bleeding and thromboembolic risk of patients treated with these molecules
The main objective of this study is to study the relation between polymorphisms of the ABCB1 gene that codes for Pgp and plasma concentrations of NOACs in patients treated for a hemorrhagic or thromboembolic complication occurring under NOAC therapy
Secondary objectives are to evaluate the distribution of ABCB1 polymorphisms among the various hemorrhagic risk factors and to compare the frequency of the polymorphism in patients from the study population vs the general population
Dabigtran rivaroxaban and apixaban are known substrates of P-glycoprotein Pgp Pgp activity can be affected by pharmacological inducing or inhibiting agents This can lead to a significant change in the pharmacokinetics of NOACs with a decrease or increase respectively in the level of intestinal absorption leading to respectively reduced or increased plasma concentrations of the drug Furthermore there exist genetic mutations of Pgp presenting in particular a lower level of activity than the non-mutated protein We hypothesized that the polymorphisms mutations of the ABCB1 gene that codes for Pgp could influence plasma concentrations of dabigatran rivaroxaban and apixaban and consequently impact on the concentration of NOACs and as a corollary on the bleeding and thromboembolic risk of patients treated with these molecules
The main objective of this study is to study the relation between polymorphisms of the ABCB1 gene that codes for Pgp and plasma concentrations of NOACs in patients treated for a hemorrhagic or thromboembolic complication occurring under NOAC therapy
Secondary objectives are to evaluate the distribution of ABCB1 polymorphisms among the various hemorrhagic risk factors and to compare the frequency of the polymorphism in patients from the study population vs the general population
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None