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

NCT02933697 | Completed Phase 3 DMC

• 1 other identifier: AXADIA - AFNET 8
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation; End-stage Kidney Disease

Keywords

Atrial Fibrillation; Kidney disease; Anticoagulation

Outcome Measures

Primary Outcomes (1)

• Assess the safety of the factor Xa inhibitor apixaban versus a vitamin-K antagonist 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 as well as specific bleedings in dialysis patients (e.g., after shunt removal) on anticoagulation.

  1-60 months

Secondary Outcomes (1)

• 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

Study Arms (2)

Apixaban

ACTIVE COMPARATOR

2.5 mg apixaban twice daily for 1 to 60 months

Drug: Apixaban

Vitamin-K antagonists (Phenprocoumon)

ACTIVE COMPARATOR

Phenprocoumon by INR (Target: 2.0-3.0) treatment for 1 to 60 months

Drug: Phenprocoumon

Interventions

Apixaban DRUG

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.

Also known as: Eliquis

Apixaban

Phenprocoumon DRUG

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.

Also known as: Marcumar

Vitamin-K antagonists (Phenprocoumon)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Atrial Fibrillation Network: lead
• Bristol-Myers Squibb: collaborator
• Pfizer: collaborator

Study Sites (1)

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Related Publications (2)

• Reinecke H, Engelbertz C, Bauersachs R, Breithardt G, Echterhoff HH, Gerss J, Haeusler KG, Hewing B, Hoyer J, Juergensmeyer S, Klingenheben T, Knapp G, Christian Rump L, Schmidt-Guertler H, Wanner C, Kirchhof P, Goerlich D. A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study. Circulation. 2023 Jan 24;147(4):296-309. doi: 10.1161/CIRCULATIONAHA.122.062779. Epub 2022 Nov 6.

  PMID: 36335915 DERIVED

• Reinecke H, Jurgensmeyer S, Engelbertz C, Gerss J, Kirchhof P, Breithardt G, Bauersachs R, Wanner C. Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study. BMJ Open. 2018 Sep 10;8(9):e022690. doi: 10.1136/bmjopen-2018-022690.

  PMID: 30206088 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Kidney Failure, Chronic; Kidney Diseases

Interventions

apixaban; Phenprocoumon

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Holger Reinecke, Prof. Dr.

  Universitätsklinikum Münster

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 14, 2016
• Study Start: June 20, 2017
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: September 27, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)