Study of direct oral anticoagulants (medications that help prevent blood clots) in lung transplant patients
| ISRCTN | ISRCTN10003031 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10003031 |
| Secondary identifying numbers | MH 001 |
- Submission date
- 27/11/2023
- Registration date
- 11/07/2024
- Last edited
- 11/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Haematological Disorders
Plain English summary of protocol
Background and study aims.
Direct oral anticoagulants (DOAC) have transformed the landscape of oral anticoagulant therapy for almost a decade. They are increasingly used in clinical practice, mainly for stroke prevention in atrial fibrillation and the treatment of venous thrombosis.
Venous thrombosis is a common complication after lung transplantation and 25% of lung transplant patients also develop atrial flutter or fibrillation. Oral anticoagulation is therefore often necessary in these patients.
DOAC pharmacology may be affected by physiological changes that occur after lung transplantation, and they are subject to some interactions with drugs given to prevent rejection, which have been little studied. This raises questions about the optimal management of anticoagulant therapy in lung transplant patients, which we are regularly facing in our clinical practice.
The main objective of the study will be to describe the pharmacology of DOAC in lung transplant patients. A secondary objective will be to evaluate clinical outcomes (bleeding and thrombosis) during a 12-months follow-up. Taken together, these data will answer the question: “How best can we safely use DOAC in lung transplant patients?”.
Who can participate?
Any adult lung transplant patient taking a direct oral anticoagulant (apixaban, dabigatran etexilate, edoxaban, or rivaroxaban) for (i) the treatment and secondary prevention of VTE or (ii) stroke prevention in NVAF may participate. However, they must be able to come to the CHU UCL Namur for 24 hours to have the necessary blood samples taken.
What does the study involve?
This study involves taking several blood samples over 24 hours to establish the pharmacological profile of DOACs in lung transplant recipients.
What are the possible benefits and risks of participating?
This is an observational study with no direct benefit to participants. Improved knowledge of the pharmacology of DOAC in lung transplant patients will help to improve their use in this population in the future.
The potential harm to participants is no different from that of a conventional blood collection (e.g., hematoma or transient pain at the puncture site).
Where is the study run from?
CHU UCL Namur in Belgium.
When is the study starting and how long is it expected to run for?
August 2021 to November 2025.
Who is funding the study?
Fonds de la Recherche Scientifique - FNRS (Belgium).
Who is the main contact?
Dr Michael Hardy, michael.hardy@uclouvain.be
Contact information
Public, Scientific, Principal Investigator
CHU UCL Namur, Service d'Anesthésiologie
Avenue Docteur G. Thérasse, 1
5530 - Yvoir - Belgium
Yvoir
5530
Belgium
 ORCID ID |
0000-0001-6701-9417 |
|---|---|
| Phone | +32 81 42 39 13 |
| michael.hardy@uclouvain.be |
Study information
| Study design | Single-centre prospective observational cohort study with a 12-month follow-up period. |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Treatment, Safety, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Pharmacokinetics and pharmacodynamics of direct oral anticoagulants in lung transplant patients: a prospective study |
| Study acronym | ATRAP |
| Study objectives | The main objective of the study is to describe the pharmacokinetic and pharmacodynamic profile of direct oral anticoagulants (DOAC) in lung transplant patients. A secondary objective is to evaluate clinical outcomes (bleeding and thromboembolic events) during follow-up. Taken together, these data will answer the question: "How best can we safely use DOAC in lung transplant patients?". |
| Ethics approval(s) |
Approved 01/03/2022, Ethics Committee of the CHU UCL Namur (Avenue Docteur G. Thérasse, 1, Yvoir, 5530, Belgium; +32 81 42 21 11; comite.ethique.g@chuuclnamur.uclouvain.be), ref: B0392022000001 |
| Health condition(s) or problem(s) studied | Direct oral anticoagulant use in lung transplant patients |
| Intervention | Pharmacokinetic study Apixaban, edoxaban and rivaroxaban plasma levels will be estimated using a calibrated chromogenic anti-Xa assay, the STA®-Liquid anti-Xa (Diagnostica Stago, Asnière, France). Dabigatran plasma levels will be estimated with an ecarin-based assay (STA®-ECA II, Diagnostica Stago). Pharmacodynamic study: Thrombin generation will be assessed using the ST Genesia analyser and STGDrugScreen® and STGThromboScreen® reagent (Diagnostica Stago®, Asnière, France). Thrombin generation at time 0 will also be measured withThromboScreen® reagent after DOAC removal using the DOAC-Stop® system (Haematex, Sydney, Australia) to assess the thrombin generation underlying DOAC. Pharmacogenetic study: The single nucleotide polymorphism (SNP) CYP3A5*3 (rs776746), known to influence tacrolimus dose requirement, will be screened. |
| Intervention type | Other |
| Primary outcome measure | Pharmacokinetic study: Concentration-time data will be analyzed using non-compartmental PK to derive PK parameters. DOAC concentrations will be measured in the morning just before DOAC intake (T0), then 1, 2, 3, 4, 6 and 8 hours after DOAC intake. Whenever possible, DOAC concentrations will also be measured the next morning just before DOAC intake (T24) to assess inter-individual variability. Apixaban, edoxaban and rivaroxaban plasma concentrations will be estimated using a calibrated chromogenic anti-Xa assay, the STA®-Liquid anti-Xa (Diagnostica Stago, Asnière, France), using dedicated calibrators from Stago. Dabigatran plasma levels will be estimated with an ecarin-based assay (STA®-ECA II, Diagnostica Stago). 1. Peak concentration (Cmax) 2. Time to reach peak concentration (Tmax) 3. Area under the concentration curve (AUC) extrapolated to infinity 4. The terminal elimination half-life 5. The apparent volume of distribution (Vd/F) 6. The apparent clearance (CL/F). Pharmacodynamic study: Thrombin generation will be measured at through (just before DOAC intake) and at peak (3 hours after DOAC intake) on the ST-Genesia system with STG-DrugScreen and STG-ThromboScreen reagent and the following parameters will be evaluated: 1. Lag time 2. Peak height 3. Time to peak 4. Endogenous thrombin potential (ETP) 5. Velocity index |
| Secondary outcome measures | Clinical outcomes during the 12-month follow-up period (or until the end of the study, depending on which comes first) measured using patient records: 1. Any documented thromboembolic event 2. Any documented bleeding event |
| Overall study start date | 24/08/2021 |
| Completion date | 02/11/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | Both |
| Target number of participants | 15 |
| Key inclusion criteria | 1. ≥ 18 years old; 2. Medical history of lung transplant; 3. DOAC prescription (apixaban, dabigatran etexilate, edoxaban or rivaroxaban) for (i) the treatment and secondary prevention of VTE or (ii) stroke prevention in NVAF. 4. DOAC taken for at least three days. 5. Both inpatients and outpatients are considered for inclusion. |
| Key exclusion criteria | Patient hospitalized in intensive care unit at inclusion. |
| Date of first enrolment | 02/11/2022 |
| Date of final enrolment | 02/11/2024 |
Locations
Countries of recruitment
- Belgium
Study participating centre
Yvoir
5530
Belgium
Sponsor information
Hospital/treatment centre
Rue du Docteur G. Thérasse, 1
Yvoir
5530
Belgium
| Phone | +32 81 42 21 11 |
|---|---|
| francois.mullier@chuuclnamur.uclouvain.be | |
| Website | https://www.chuuclnamur.be/ |
"ROR" |
https://ror.org/00ntbvq76 |
Funders
Funder type
Government
Government organisation / Local government
- Alternative name(s)
- F.R.S. - FNRS, Fund for Scientific Research - FNRS, Belgian National Fund for Scientific Research, FNRS
- Location
- Belgium
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal. |
| IPD sharing plan | Storing in a publicly available repository. |
Editorial Notes
11/01/2024: Trial's existence confirmed by Ethics Committee of the CHU UCL Namur
