AnticoagulantsPgp NACONCT02103101
Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events
A study testing Measurement of Plasma Concentrations of NOACs and Identification of ABCB1 polymorphisms coding for P-gp in people with Anticoagulants and Thromboembolism, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Anticoagulants, Thromboembolism, Hemorrhage
- What is being tested?
- Measurement of Plasma Concentrations of NOACs and Identification of ABCB1 polymorphisms coding for P-gp
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteFrance
- Study dates
- 13 Nov 2014to 31 Oct 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged >18 and <80 years of age
- Patients admitted to the University Hospital of Besancon for a serious adverse event (major bleeding complication or thrombo-embolic event) occurring under treatment with any one of the three commercially available new oral anticoagulant agents (rivaroxaban, apixaban or dabigatran).
- Patients must have social security coverage.
- Patients must provide written informed consent.
Who cannot join
- Hemorrhagic complication from causes not related to drug therapy
- Hemorrhagic complication occurring in patients not treated with oral anticoagulants at the time of the event
- Thrombo-embolic complication occurring in patients not treated with oral anticoagulants at the time of the event
- Legal incapacity, patients under judicial protection
- Patients with no social security coverage
- Patients unlikely to be compliant or anticipated by the investigator to be non-compliant with the study requirements
- Patients in a wash-out period further to participation in a previous clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Anticoagulants, Thromboembolism, Hemorrhage
- Being tested
- Measurement of Plasma Concentrations of NOACs, Identification of ABCB1 polymorphisms coding for P-gp
- Keywords
- polymorphism, ABCB1, P-glycoprotein, oral anticoagulant, dabigatran, apixaban, rivaroxaban, hemorrhagic complication, thrombo-embolism, serious adverse event
- Medical subject headings
- Thromboembolism, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measurement of Plasma Concentrations of NOACsOther
Plasma concentrations of dabigatran, rivaroxaban or apixaban will be measured using High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). Blood samples will be taken in an EDTA tube and rapidly centrifugated. Plasma will be aliquoted and frozen at minus 80 degrees Celsius for later analysis.
Identification of ABCB1 polymorphisms coding for P-gpGenetic
To investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167).
| Study group | Role | What they receive |
|---|---|---|
| Study cohort | Other | Measurement of Plasma Concentrations of NOACs Identification of ABCB1 polymorphisms coding for P-gp
All patients aged over 18 and less than 80 years admitted for a serious adverse event (bleeding or thrombo-embolic complication) while under treatment with any of the following oral anticoagulant agents: dabigatran, rivaroxaban or apixaban. Blood samples will be drawn to measure plasma concentrations of the oral anticoagulant agent at the time of the adverse event, and presence of polymorphisms of ABCB1 will be investigated. Receives: Other: Measurement of Plasma Concentrations of NOACs; Genetic: Identification of ABCB1 polymorphisms coding for P-gp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of plasma concentrations of new oral anticoagulant agents
Plasma concentrations of dabigatran, rivaroxaban or apixaban will be measured using High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). Blood samples will be taken in an EDTA tube and rapidly centrifugated. Plasma will be aliquoted and frozen at minus 80 degrees Celsius for later analysis.
Measured: 0 days (at inclusion)
Identification of polymorphisms of the gene ABCB1 coding for P-gp
To investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167).
Measured: 0 days (at inclusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2014 (estimated)
- Study start13 Nov 2014
- Primary completion31 Oct 2017
- Study completion31 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnticoagulantsStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Collaborators
- Etablissement Français du Sang
- Responsible party
- Sponsor
- Investigators
- Nicolas F Meneveau, MD, PhD, Principal investigator, Centre Hospitalier Universitaire de Besancon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02103101
- Sponsor's protocol ID
- Pgp NOAC
- Acronym
- Pgp NACO
- Status last verified
- Jul 2018
- First submitted
- 31 Mar 2014
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events
- ClinicalTrials.gov ID
- NCT02103101
- Acronym / sponsor ID
- Pgp NACO / Pgp NOAC
- Conditions
- Anticoagulants, Thromboembolism, Hemorrhage
- Keywords
- polymorphism, ABCB1, P-glycoprotein, oral anticoagulant, dabigatran, apixaban, rivaroxaban, hemorrhagic complication
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Collaborators
- Etablissement Français du Sang
- Study start
- 13 Nov 2014 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 31 Oct 2017 (actual)
- First posted
- 3 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study cohort | Other | Other: Measurement of Plasma Concentrations of NOACs, Genetic: Identification of ABCB1 polymorphisms coding for P-gpMeasurement of Plasma Concentrations of NOACs Identification of ABCB1 polymorphisms coding for P-gp All patients aged over 18 and less than 80 years admitted for a serious adverse event (bleeding or thrombo-embolic complication) while under treatment with any of the following oral anticoagulant agents: dabigatran, rivaroxaban or apixaban. Blood samples will be drawn to measure plasma concentrations of the oral anticoagulant agent at the time of the adverse event, and presence of polymorphisms of ABCB1 will be investigated. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged >18 and <80 years of age
- Patients admitted to the University Hospital of Besancon for a serious adverse event (major bleeding complication or thrombo-embolic event) occurring under treatment with any one of the three commercially available new oral anticoagulant agents (rivaroxaban, apixaban or dabigatran).
- Patients must have social security coverage.
- Patients must provide written informed consent.
Key exclusion criteria (7 listed)
- Hemorrhagic complication from causes not related to drug therapy
- Hemorrhagic complication occurring in patients not treated with oral anticoagulants at the time of the event
- Thrombo-embolic complication occurring in patients not treated with oral anticoagulants at the time of the event
- Legal incapacity, patients under judicial protection
- Patients with no social security coverage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measurement of Plasma Concentrations of NOACsPlasma concentrations of dabigatran, rivaroxaban or apixaban will be measured using High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). Blood samples will be taken in an EDTA tube and rapidly centrifugated. Plasma will be aliquoted and frozen at minus 80 degrees Celsius for later analysis. | Other | Study cohort |
| Identification of ABCB1 polymorphisms coding for P-gpTo investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167). | Genetic | Study cohort |
Primary outcome
Measurement of plasma concentrations of new oral anticoagulant agents
Time frame: 0 days (at inclusion)
Plasma concentrations of dabigatran, rivaroxaban or apixaban will be measured using High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). Blood samples will be taken in an EDTA tube and rapidly centrifugated. Plasma will be aliquoted and frozen at minus 80 degrees Celsius for later analysis.
Identification of polymorphisms of the gene ABCB1 coding for P-gp
Time frame: 0 days (at inclusion)
To investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
Related trials for Anticoagulants
RecruitingPhase 3
Thrombolysis in Factor Xa-inhibitors Trial
Stroke, Stroke (in Patients With Atrial Fibrillation)
Not yet recruitingPhase 4
Perioperative Dutasteride for Hemorrhage Control in Bipolar TURP Under Anticoagulation.
Benign Prostatic Hyperplasia, Postoperative Hemorrhage
Not yet recruitingObservational study
High-risk Antithrombotic Drugs at Discharge and Consultation for Hemorrhagic or Thromboembolic Events in the Emergency Department
Acute Disease
RecruitingPhase 3
Testing a New Treatment Strategy to Improve Secondary Stroke Prevention for Older Adults: The STROKE75+ Trial
Stroke, Ischemic
Not yet recruitingObservational study
Changes in the Etiology of Acute Limb Ischemia in the DOAK Era
Acute Limb Ischemia, Anticoagulants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas F Meneveau, MD, PhD principal investigator
Centre Hospitalier Universitaire de Besancon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Measurement of Plasma Concentrations of NOACs and Identification of ABCB1 polymorphisms coding for P-gp in people with Anticoagulants and Thromboembolism, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of plasma concentrations of new oral anticoagulant agents (time frame: 0 days (at inclusion)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2018.