Safety and Efficacy of Apixaban Versus Warfarin in Peritoneal Dialysis Patients With Non Valvular Atrial Fibrillation: a Prospective, Randomised, Open-label, Blinded End-point Trial (APIDP2)

NCT06045858 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: 23-1642023-507544-37-00
• Study Type: interventional
• Target: 178
• Locations: 0 countries
• Sites: N/A

Brief Summary

Introduction: Several randomised controlled trials have demonstrated that novel oral anticoagulants (NOACs) are safer compared to vitamin K antagonists for the management of non valvular atrial fibrillation (NVAF) to prevent thromboembolic events, in the general population. There is a growing interest in the use of apixaban in patients with End-Stage Renal-Disease (ESRD) undergoing peritoneal dialysis but there is a lack of randomised data in this population. Design: APIDP2 is a prospective parallel randomised, open-label, blinded endpoint trial. Participants: Patients with ESRD undergoing chronic Peritoneal Dialysis who have NVAF. Setting: A total of 178 participants will be recruited from 20 French peritoneal dialysis centers. Intervention: Eligible patients will be randomly assigned to receive either apixaban at a reduced dose 2.5mg twice daily (dose determined with the previous pharmacokinetic study APIDP1 of apixaban in PD patients) or dose-adjusted to INR target \[2-3\] coumadin therapy. Anticoagulation to prevent thromboembolic events will be initiated or changed according to the randomisation for a duration of one year. The primary outcome is a major or clinically relevant non-major bleeding from randomisation up to Month 12, assessed according to ISTH score. Secondary outcomes encompass an efficacy composite criterion combining stroke or TIA, cardiovascular death, and thrombosis including myocardial infarction cumulated at 12 months. Bleeding events will be also classified according to GUSTO and TIMI criteria and pharmacodynamics outcomes will evaluate the time within the INR target range of \[2-3\] in the warfarin arm over one year, and AntiXa apixaban activity in case of bleeding events and at 1, 6, and 12 months of follow-up in the apixaban arm. Primary outcome analysis: To demonstrate that apixaban is safer than warfarin at one year, assuming two interim analyses after 60 and 118 patients, a bilateral alpha risk of 5% and a power of 80%, 178 patients are needed in this randomised trial (effect size found in the ARISTOTLE study among patients with CrCl \[25-30\]ml/min), i.e. 89 patients per group.

Conditions

Atrial Fibrillation; Peritoneal Dialysis Complication

Keywords

peritoneal dialysis; atrial fibrillation; anticoagulation; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Safety primary criterion

  at least one event for each participant ISTH major or clinically relevant non-major bleeding cumulated at 12 months

  0-12 months

Secondary Outcomes (1)

• Composite efficacy criterion

  0-12 months

Study Arms (2)

Warfarin

ACTIVE COMPARATOR

Warfarin (Coumadine): INR target \[2.0-3.0\]

Drug: Anticoagulation Agents

Apixaban

EXPERIMENTAL

Apixaban (Eliquis) at 2.5mg, per os, twice a day

Drug: Anticoagulation Agents

Interventions

Anticoagulation Agents DRUG

anticoagulation in peritoneal dialysis patients with non valvular atrial fibrillation during one year

Apixaban; Warfarin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, age at least 18 years, in ESRD treated with peritoneal dialysis for ≥ 3 months
• Patients with a history of non valvular AF treated by oral anticoagulation or patients initiating oral anticoagulation for a diagnosis of non valvular AF
• CHA2DS2-VASc score of ≥ 2.
• For women of childbearing age who are sexually active, use of an effective method of contraception for up to 10 days after the end of treatment and a negative blood pregnancy test at enrollment.
• Signature of informed consent

You may not qualify if:

• Not considered by the treating physician(s) to be candidates for oral anticoagulation (for example, hemoglobin \<8.5g/dL, history of intracranial hemorrhage, active bleeding, recent gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment, or anaphylactic reaction to apixaban)
• Moderate or severe mitral stenosis
• Patient treated with haemodyalisis
• Conditions other than non valvular AF that require anticoagulation such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism
• Life expectancy \< 3 months
• Anticipated kidney transplant within the next 3 months
• Individuals covered by Articles L1121-5 to L1121-8 of the French Public Health Code (corresponding to all protected persons: pregnant women, postpartum women, breastfeeding mothers, individuals deprived of their liberty by judicial or administrative decision, minors, individuals under legal protection such as guardianship or trusteeship).
• Women of childbearing age not using a highly effective contraceptive method during the study and up to 10 days after the end of treatment.
• Use of potent inducers of CYP3A4 (particularly rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort (Hypericum perforatum)).
• Use of CYP3A4 and P-gp inhibitors, particularly azole antifungals (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole), HIV protease inhibitors, clarithromycin, and erythromycin.
• Contraindication to anticoagulant treatment, such as antiphospholipid syndrome.

Sponsors & Collaborators

• University Hospital, Caen: lead

Related Publications (1)

• Ficheux M, Peyro-Saint-Paul L, Balayn D, Lecrux B, Brossier M, Morin A, Lanot A, Peron C, Boulanger M, Brionne M, Beygui F, Parienti JJ, Lobbedez T, Bechade C. Safety and efficacy of apixaban versus warfarin in peritoneal dialysis patients with non-valvular atrial fibrillation: protocol for a prospective, randomised, open-label, blinded endpoint trial (APIDP2). BMJ Open. 2024 Sep 20;14(9):e089353. doi: 10.1136/bmjopen-2024-089353.

  PMID: 39306346 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Anticoagulants

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Laure Peyro-saint-paul

CONTACT

233 31065342; peyrosaintpaul-l@chu-caen.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: a Haybittle sequential plan (PROC SEQDESIGN, SAS 9.4) with decision rule for better safety (larger than expected effect)

Study Record Dates

• First Submitted: September 4, 2023
• First Posted: September 21, 2023
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: August 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL