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

September 26, 2022 updated by: Atrial Fibrillation Network

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

108

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Münster, Germany, 48149
        • Universitatsklinikum Munster

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Apixaban
2.5 mg apixaban twice daily for 1 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 1 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the safety of the factor Xa inhibitor apixaban versus a vitamin-K antagonist phenprocoumon in patients with NVAF and ESKD on hemodialysis.
Time Frame: 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.
1-60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
1-60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Atrial Fibrillation Network

Collaborators

Bristol-Myers Squibb
Pfizer

Investigators

  • Principal Investigator: Holger Reinecke, Prof. Dr., Universitatsklinikum Munster

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2017

Primary Completion (Actual)

July 31, 2022

Study Completion (Actual)

July 31, 2022

Study Registration Dates

First Submitted

October 7, 2016

First Submitted That Met QC Criteria

October 12, 2016

First Posted (Estimate)

October 14, 2016

Study Record Updates

Last Update Posted (Actual)

September 27, 2022

Last Update Submitted That Met QC Criteria

September 26, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AXADIA - AFNET 8

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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