Compare Apixaban and Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD)

• Status: Recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The Study is an open-labeled, randomized controlled trial, phase IIIb. Its objective is to assess the safety of the factor Xa inhibitor apixaban versus the vitamin-K antagonist (VKA) phenprocoumon in patients with NVAF and ESKD on hemodialysis. The safety will be assessed by means of the incidence of major and clinically relevant, non-major bleeding on anticoagulation.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Atrial Fibrillation Network; German Atrial Fibrillation Network
• Collaborators: Bristol-Myers Squibb; Pfizer
• Treatments: Apixaban; Phenprocoumon; Vitamin K; Vitamins

Criteria

Inclusion Criteria:

• End-stage kidney disease (ESKD) with chronic hemodialysis treatment 3 times per week (with about at least 3.5 hours per dialysis)

• Chronic (i.e. repeated) paroxysmal, persistent or permanent atrial fibrillation (AF) or atrial flutter (AFL) documented by standard or Holter ECG on at least 2 separate days before (or apart from) hemodialysis procedures

• Increased risk of stroke or systemic embolism identified by a CHA2DS2-VASc score of 2 or more as an indication for oral anticoagulation

• Patients with ischemic stroke that meet the above criteria, can be included after more than 3 months if not severely handicapped (modified Rankin scale 0 or 1 of 6, i.e. no symptoms or no significant disability and able to carry out all usual activities, despite some symptoms (Farrell, Godwin, Richards, and Warlow (1991))

• Males and females, aged 18 or older

Exclusion Criteria:

• AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis)

• Patients with a new onset of hemodialysis within the last 3 months

• Clinically significant (moderate or severe) aortic and mitral stenosis

• Conditions other than AF or AFL that require chronic anticoagulation (e.g., a prosthetic mechanical heart valve).

• Active infective endocarditis

• Any planned interventional or surgical AF or AFL ablation procedure

• Any active bleeding

• A serious bleeding event in the previous 6 months before screening

• Inadequately controlled (HbA1c levels >8.5%) or untreated diabetes

• History of malignant neoplasms at high risk of current bleeding (see summary of product characteristics (SmPC) of study drugs)

• Known indication for treatment with NSAIDs (see SmPC of study drugs) - acetylsalicylic acid (ASA) up to 100 mg per day is allowed

• Known Antiphospholipid Syndrome requiring anticoagulation

• Impaired liver function e.g., caused by active infection with HIV, HBV or HCV, hepatitis or other liver damage (No limits for ALT and AST values are defined in this study protocol, although mentioned in the SmPC because they are frequently elevated in dialysis patients. In case of clinically relevant increase of ALT or AST level, patient's eligibility is to be decided by the responsible investigator)

• Any type of stroke within 3 months prior to baseline

• Other indication for anticoagulation than AF or AFL

• Valvular heart disease requiring surgery

• A high risk of bleeding (e.g., active peptic ulcer disease, a platelet count of <100,000 per cubic millimeter or hemoglobin level of <8 g per deciliter)

• Documented hemorrhagic tendencies or blood dyscrasias

• Current alcohol or drug abuse

• Life expectancy of less than 1 year

• Indication for dual platelet inhibition at baseline (ASA ≤ 100 mg/day is allowed, clopidrogel is excluded at any dose).

• Active infection or symptoms suggestive of COVID-19 infection.