Clinical trial NCT05410275: Chronic Anticoagulation With a Reduced Dose Regimen of Rivaroxaban in End-stage Renal Disease Patients
Official title: Chronic Anticoagulation in End-stage Renal Disease Patients: Pharmacokinetics and Pharmacodynamic of a Reduced Dose Regimen of Rivaroxaban
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Hemodialysis Patients
Keywords: Kidney Diseases
Therapeutic drug monitoring
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2022-06-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Atrial fibrillation is the most frequent cardiac rhythm disorder and its prognosis is essentially marked by the risk of embolic events. Its treatment is based on long-term oral anticoagulant therapy according to the risk of embolic events assessed by risk scores such as the CHA2DS2-Vasc score, but this prescription is associated with a risk of hemorrhagic events that must be taken into consideration when deciding on the treatment for a given patient. There are two categories of validated oral anticoagulant treatments for the prevention of embolic events in atrial fibrillation: antivitamin K agents, which have long been the reference treatment but are restrictive and difficult to use because of a narrow therapeutic window, and direct oral anticoagulants, which are now the first-line treatment but have not been evaluated in phase II and III studies in patients with severe renal failure. End-stage renal disease (clearance \<15 mL/min/1.73m2), particularly at the dialysis stage, is a risk factor for cardiovascular disease in its own right, and a significant number of patients develop atrial fibrillation. Given the co-morbidities associated with renal failure, in particular hypertension, patients with renal failure undergoing dialysis and suffering from atrial fibrillation are generally at a higher risk of embolism than patients without renal failure, but also at a higher risk of bleeding. Thus, if the indication for prescribing oral anticoagulant therapy is clear in this population, the associated bleeding complications are also more frequent and more serious in these patients who have regular vascular accesses in the context of hemodialysis. There is thus a real need for reliable therapeutic alternatives with a better benefit/risk ratio than antivitamins K.

Translated with www.DeepL.com/Translator (free version)

Detailed description: Chronic dialysis patients are a special population because the constraints linked to their disease (3 dialyses per week) make them a captive population that nephrologists know perfectly well. If the identification of the subjects to be included does not pose any problem, it is more their adherence to the project which is likely to be more difficult because it implies additional constraints in these patients with potentially many comorbidities.

This proof-of-concept study will identify the dose of rivaroxaban with the best pharmacokinetic/ pharmacodynamic profile in chronic hemodialysis patients. It will then be possible to envisage a larger study of the type of a national Hospital Clinical Research Program (PHRC) in order to evaluate the dose of rivaroxaban chosen in hemodialysis patients with atrial fibrillation with an indication for oral anticoagulation on the basis of morbidity-mortality criteria in comparison with treatment with antivitamins K that is well conducted.

Eligibility criteria: Inclusion Criteria:

* Adult patient ≥ 18 years of age,
* Chronic hemodialysis patient for at least 3 months,
* Affiliated or beneficiary of a social security plan,
* Having signed a written and informed consent.

Exclusion Criteria:

* Any indication for long-term oral anticoagulation (atrial fibrillation, venous thromboembolic disease, mechanical valve prostheses, intracardiac thrombosis, etc.)
* Double anti-platelet aggregation for any reason or an aspirin dose greater than 160 mg/day
* Uncontrolled hypertension (BP \> 180/110 mmHg)
* Ischemic stroke within 30 days prior to inclusion
* History of major unprovoked hemorrhage (leading to hospitalization or transfusion) regardless of age
* Surgery within 30 days prior to inclusion
* High-risk bleeding condition in addition to renal failure (such as known coagulation disorder, thrombocytopenia (\< 100G/L), active neoplasia of the digestive or urinary tract, or presence of intracranial vascular malformation)
* Severe hepatic impairment
* Use of strong CYP3A4 inducers, including rifampin, St. John's Wort, carbamazepine, phenytoin, phenobarbital
* Non-compliant patients
* Pregnant or breastfeeding women, women of childbearing age without effective contraception
* Contraindication to the administration of an anticoagulant treatment such as anti-phospholipid antibody syndrome
* Known allergy to rivaroxaban or to one of its excipients (lactose monohydrate)
* Patients under guardianship or conservatorship
* Patients already participating in an ongoing study or who have participated in a study that ended less than 30 days prior to the inclusion date.

Primary outcomes:
measure: Pharmacodynamics of 3 reduced dose regimen of rivaroxaban (5 mg/day, 10 mg/day, or 15 mg/day)
timeFrame: 1 month
measure: Pharmacokinetics of 3 reduced dose regimen of rivaroxaban (5 mg/day, 10 mg/day, or 15 mg/day)
timeFrame: 1 month
Secondary outcomes:
measure: Hemorrhagic risk assessment of 3 reduced dose regimen of rivaroxaban (5 mg/day, 10 mg/day, or 15 mg/day)
timeFrame: 1 month
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital of TOURS
name: Fabrice IVANES, MD-PhD
role: STUDY_DIRECTOR
References: