NCT02103101: Pgp NACO

Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events

Completed NA Last updated 18 July 2018

What this trial tests

NA trial testing Measurement of Plasma Concentrations of NOACs in Anticoagulants in 68 participants. Completed in 31 October 2017.

Timeline

13 November 2014

Primary endpoint
31 October 2017

31 October 2017

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Besancon
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	68
Start date	13 November 2014
Primary completion	31 October 2017
Estimated completion	31 October 2017
Sites	1 location across France

Drugs / interventions tested

• Measurement of Plasma Concentrations of NOACs
• Identification of ABCB1 polymorphisms coding for P-gp

Conditions studied

• Anticoagulants — all drugs for Anticoagulants →
• Thromboembolism — all drugs for Thromboembolism →
• Hemorrhage — all drugs for Hemorrhage →

Sponsor

Centre Hospitalier Universitaire de Besancon

Who can join

Adults 18 to 80, any sex, with Anticoagulants or Thromboembolism. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. The impact of <i>ABCB1</i> (rs1045642 and rs4148738) and <i>CES1</i> (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty.
   Sychev DA, Levanov AN, Shelekhova TV, Bochkov PO, et al · · 2018 · cited 39× · PMID 30100750 · DOI 10.2147/pgpm.s169277