|- candidate number||28515|
|- NTR Number||NTR6989|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||31-jan-2018|
|- Secondary IDs||17-120 MEC|
|- Public Title||The effect of body weight on the medicine concentrations of dabigatran,
edoxaban, apixaban and rivaroxaban in blood.|
|- Scientific Title||The effect of body weight on trough concentrations of DOACs in patients.|
|- ACRONYM||BC_DOAC study|
|- hypothesis||Body weight has an effect at the trough concentrations of DOACs in patients.|
|- Healt Condition(s) or Problem(s) studied||Body-weight, DOAC, Trough concentration|
|- Inclusion criteria||- Male or female ≥ 18 years|
- Treated with a DOAC (rivaroxaban, dabigatran, apixaban, edoxaban) in a therapeutic or prophylactic dosage for at least 5 days
- eGFR > 50 ml/min
- Is not mentally disabled
- Good understanding of the Dutch language
- Written informed consent
|- Exclusion criteria||- The use of relevant co-medication: Ketoconazole, Posaconazole, Voricanazole , Itraconazole , Fluconazole, HIV protease inhibitors, Ticagrelor , Verapamil , Diltiazem (except dabigatran) , Amiodarone , Quinidine, Cyclosporin, Tacrolimus, Clarithromycin, Erythromycin, Carbamazepine, Rifampicin, St John¡¯s wort, Phenytoin
|- mec approval received||yes|
|- multicenter trial||no|
|- planned startdate ||1-feb-2018|
|- planned closingdate||1-feb-2019|
|- Target number of participants||160|
|- Interventions||Patients will only use the licensed DOACs (Eliquis®, Xarelto® Lixiana® and Pradaxa®) as standard care prescribed by their physician. No intervention will take place, only DOAC trough concentrations will be measured in patients. For this reason patients have to provide a one-time blood sample.|
|- Primary outcome||The primary objective of this study is to investigate the effect of body weight on the trough concentrations of DOACs.|
|- Secondary outcome||- To investigate the effect of body weight on anti-Factor Xa (FXa) activity for apixaban, rivaroxaban and edoxaban. |
- To investigate the effect of body weight on anti-Factor IIa (FIIa) activity for dabigatran.
|- Timepoints||The inclusion will take place from February 2018 till February 2019 in the Haga Teaching Hospital. Blood samples will be analysed by the department of clinical chemistry LabWest for anti-FXa activity or anti-FIIa activity and renal function. The trough concentration of the DOAC will be analysed by the Central Hospital Pharmacy (AHZ) laboratory.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| J.M. Borst|
|- CONTACT for SCIENTIFIC QUERIES|| J.M. Borst|
|- Sponsor/Initiator ||Haga Teaching Hospital, The Hague, Central Hospital Pharmacy The Hague|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale: |
High trough concentrations of direct oral anticoagulants (DOACs) are related to a higher bleeding risk while low trough concentrations increase the risk of an ischemic stroke / systemic embolic event (SEE) risk. Different factors, including body weight, may have an impact on the plasma concentrations of DOACs. Dose reductions for the DOAC edoxaban are recommended for patients with a body weight of less than 60 kg and for apixaban when patients with atrial fibrillation have two or more of the following critiria: body weight less than 60 kg, serum creatine > 133 umol/L or age > 80 year. This is in contrast with the other DOACs where no dose adjustments based on body weight are recommended. It seems that there is need for further research for all DOACs to investigate if dose adjustment is recommended for patients with low or high body weight.
Objective: To investigate the effect of body weight on the trough concentrations of DOACs in patients.
Exploratory cohort study.
Patients (¡Ý 18 year) treated at the in- or outpatient clinic of the Haga Teaching Hospital who are prescribed a DOAC (rivaroxaban, dabigatran, apixaban or edoxaban).
Main study parameters/endpoints: The main study parameter is body weight and the primary endpoint is the DOAC trough concentration.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Patients using DOACs as their standard care can participate in this study. The study will take place according to the Dutch Medical Research Involving Human Subjects Act (WMO) as patients are asked to provide a one-time blood sample. Patients have to provide a written informed consent before entering the study. After providing the written informed consent a medication reconciliation interview will take place. Blood sampling for the study will be combined, if possible, with normal care so that the need for extra venepunctures will be minimalized. The risks that patients are exposed to are complications from blood sampling. To reduce complications, sampling procedures will be performed by health care professionals who are trained in these procedures.
|- Main changes (audit trail)|
|- RECORD||31-jan-2018 - 13-feb-2018|