Chronic Anticoagulation With a Reduced Dose Regimen of Rivaroxaban in End-stage Renal Disease Patients

NCT ID: NCT05410275

Last Updated: 2022-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-01
• Study Completion Date: 2024-01-01

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.

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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.

Conditions

Chronic Hemodialysis Patients

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rivaroxaban

Rivaroxaban 5 mg daily, administered orally, during 3 consecutive days. After a wash-out period of 4 days, Rivaroxaban 10 mg daily, administered orally, during 3 consecutive days.

After a wash-out period of 4 days, Rivaroxaban 15 mg daily, administered orally, during 3 consecutive days.

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

Experimental group Each patient will receive successively over 3 distinct periods the 3 doses of rivaroxaban to be evaluated, i.e., 5 mg, 10 mg, and 15 mg as a single daily dose (once daily over 3 days for each dose).

Interventions

Rivaroxaban

Experimental group Each patient will receive successively over 3 distinct periods the 3 doses of rivaroxaban to be evaluated, i.e., 5 mg, 10 mg, and 15 mg as a single daily dose (once daily over 3 days for each dose).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabrice IVANES, MD-PhD

Role: STUDY_DIRECTOR

University Hospital of TOURS

Central Contacts

Fabrice IVANES, MD-PhD

Role: CONTACT

F.IVANES@chu-tours.fr

+33247473663

Adeline FOURMY, MSc

Role: CONTACT

a.fourmy@chu-tours.fr

+33218370645

Other Identifiers

DR190242-CARD-AXA

Identifier Type: -

Identifier Source: org_study_id