Chronic anticoagulation in end-stage renal disease patients: pharmacocinetics and pharmacodynamic of a reduced dose regimen of rivaroxaban (CARD-AXA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

8 Jan 2025 → ongoing

Decision date (initial)

2024-04-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-505733-28-00

ClinicalTrials.gov

NCT05410275

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

Identify the dose of rivaroxaban (5 mg/day, 10 mg/day or 15 mg/day) with the best biological safety/efficacy profile (pharmacokinetics/phamacodynamics) in a population of chronic haemodialysis patients with no indication for oral anticoagulation

Secondary objectives 1

1. To assess the risk of bleeding associated with each dose of rivaroxaban according to the BARC (Bleeding Academy research Consortium) classification in dialysis patients

Conditions and MedDRA coding

Chronic hemodialysis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adult patient ≥ 18 years
2. Chronic haemodialysis for at least 3 months
3. Participants covered by or entitled to social security
4. Patients who have signed a written informed consent form

Exclusion criteria 17

1. Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, persons subject to a legal protection measure: guardianship or trusteeship)
2. Women of childbearing age not using a highly effective method of contraception for the duration of the study.
3. Any indication for long-term oral anticoagulation (atrial fibrillation, thromboembolic venous disease, mechanical valve prosthesis, intracardiac thrombosis, etc)
4. Double anti-platelet aggregation for any reason or a dose of aspirin greater than 160 mg per day
5. Uncontrolled arterial hypertension (BP > 180/110 mmHg)
6. Ischaemic stroke in the 30 days prior to inclusion
7. History of major unprovoked haemorrhage (leading to hospitalisation or transfusion), regardless of how long it has existed
8. Surgery in the 30 days prior to inclusion except for interventions considered to have a low risk of bleeding, such as dental care and extractions.
9. High-risk bleeding pathology in addition to renal failure, such as a known coagulation disorder, thrombocytopenia (< 100G/L), progressive neoplasia of the digestive or urinary tract, or the presence of an intracranial vascular malformation
10. Severe hepatic insufficiency
11. Use of powerful CYP3A4 inducers (in particular rifampicin, phenytoin, carbamazepine, phenobarbital or St John's wort (Hypericum perforatum))
12. Use of treatments that inhibit CYP3A4 and gp-P, in particular azole antifungals (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, HIV protease inhibitors, clarithromycin and erythromycin).
13. Contraindication to anticoagulant treatment, such as anti-phospholipid antibody syndrome
14. Contraindications to the administration of rivaroxaban
15. Patient registered on the renal transplant list and refusing temporary contraindication for the duration of the study
16. Patients for whom the investigator considers that they will be unable to undergo the protocol treatment, for whatever reason
17. Patient already taking part in an ongoing study or having taken part in a study which ended less than 30 days before the inclusion date

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Area under the AUC curve (drug dosage and anti-Xa activity) for each of the 3 doses of rivaroxaban (5, 10 and 15 mg/d)

Secondary endpoints 1

1. Occurrence of bleeding events graded according to the BARC classification during the study period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours Cedex 9

Postcode

37044

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Cordinating investigator

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Cordinating investigator

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications