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

Sponsor

Atrial Fibrillation Network (Other)

Overall Status

Recruiting

CT.gov ID

NCT02933697

Collaborator

Bristol-Myers Squibb (Industry), Pfizer (Industry)

108

Enrollment

Location

Arms

72.3

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation End-stage Kidney Disease	Drug: Apixaban Drug: Phenprocoumon	Phase 3

Detailed Description

AXADIA is an investigator-driven, prospective, parallel-group, single country, multi-center phase IIIb trial to assess the safety of apixaban versus the vitamin-K antagonist phenprocoumon in patients with NVAF and ESKD on hemodialysis treatment. The trial will be conducted in about 25-30 sites in Germany.

The primary goal of this study is to assess the safety of two types of oral anticoagulants in patients with ESKD on hemodialysis with non-valvular atrial fibrillation (NVAF). The novel FXa inhibitor apixaban (at a reduced dose of 2x 2.5 mg/day) will be compared to the vitamin-K antagonist (VKA) phenprocoumon (target range: International Normalized Ratio (INR) 2.0-3.0) regarding bleeding rates during chronic administration for prevention of stroke or systemic embolism.

The primary hypothesis of the study is that oral anticoagulation with apixaban will improve the safety by significantly reducing bleeding rates in patients with ESKD on hemodialysis and NVAF compared to the VKA phenprocoumon.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety Study Assessing Oral Anticoagulation With Apixaban Versus Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD) on Chronic Hemodialysis Treatment

Actual Study Start Date :

Jun 20, 2017

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Apixaban 2.5 mg apixaban twice daily for 6 to 60 months	Drug: Apixaban Patients will be instructed to take one tablet of 2.5 mg twice daily: one tablet in the morning and one in the evening at approximately the same time every day (with about 12 hours gap) irrespective of the time of dialysis. Other Names: Eliquis
Active Comparator: Vitamin-K antagonists (Phenprocoumon) Phenprocoumon by INR (Target: 2.0-3.0) treatment for 6 to 60 months	Drug: Phenprocoumon Subjects in phenprocoumon treatment group will receive phenprocoumon individually adjusted to an INR of 2.0-3.0 as recommended in the appropriate SmPC for AF patients. Other Names: Marcumar

Arm

Intervention/Treatment

Active Comparator: Apixaban

2.5 mg apixaban twice daily for 6 to 60 months

Drug: Apixaban

Patients will be instructed to take one tablet of 2.5 mg twice daily: one tablet in the morning and one in the evening at approximately the same time every day (with about 12 hours gap) irrespective of the time of dialysis.

Other Names:

Eliquis

Active Comparator: Vitamin-K antagonists (Phenprocoumon)

Phenprocoumon by INR (Target: 2.0-3.0) treatment for 6 to 60 months

Drug: Phenprocoumon

Subjects in phenprocoumon treatment group will receive phenprocoumon individually adjusted to an INR of 2.0-3.0 as recommended in the appropriate SmPC for AF patients.

Other Names:

Marcumar

Outcome Measures

Primary Outcome Measures

Assess the safety of the factor Xa inhibitor apixaban versus a vitamin-K antagonist phenprocoumon in patients with NVAF and ESKD on hemodialysis. [1-60 months]
The safety will be assessed by means of the incidence of major and clinically relevant, non-major bleeding as well as specific bleedings in dialysis patients (e.g., after shunt removal) on anticoagulation.

Secondary Outcome Measures

Compare the efficacy of the factor Xa inhibitor apixaban with the VKA phenprocoumon regarding prevention of thromboembolic events in patients with ESKD on hemodialysis and AF [1-60 months]
The efficacy of the factor Xa inhibitor apixaban with the VKA phenprocoumon regarding prevention of thromboembolic events in patients with ESKD on hemodialysis and AF

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.