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

NCT02933697

Last updated date
Study Location
Universitätsklinikum Münster
Münster, , 48149, Germany
Contact
0049 (0) 251 980

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Atrial Fibrillation, End-stage Kidney Disease
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- End-stage kidney disease (ESKD) with chronic hemodialysis treatment 3 times per week (with about 4 hours per dialysis)

- Chronic (i.e. repeated) paroxysmal, persistent or permanent non-valvular atrial fibrillation (NVAF) 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- AF or atrial flutter 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 that require chronic anticoagulation (e.g., a prosthetic
mechanical heart valve).


- Active infective endocarditis


- Any planned interventional or surgical AF or atrial flutter 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


- 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 NVAF


- 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).

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Atrial Fibrillation, End-stage Kidney DiseaseCompare Apixaban and Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD)
NCT02933697
  1. Münster,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Compare Apixaban and Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD)
Official Title  ICMJE 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
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.
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.

A pharmacokinetic sub-study will be performed with 28 patients included in the apixaban treatment group to evaluate the systemic exposure of apixaban before and after hemodialysis session in this special population.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Atrial Fibrillation
  • End-stage Kidney Disease
Intervention  ICMJE
  • 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 Name: Elquis
  • 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 Name: Marcumar
Study Arms  ICMJE
  • Active Comparator: Apixaban
    2.5 mg apixaban twice daily for 6 to 24 months
    Intervention: Drug: Apixaban
  • Active Comparator: Vitamin-K antagonists (Phenprocoumon)
    Phenprocoumon by INR (Target: 2.0-3.0) treatment for 6 to 24 months
    Intervention: Drug: Phenprocoumon
Publications * Reinecke H, Jürgensmeyer 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 12, 2016)
222
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • End-stage kidney disease (ESKD) with chronic hemodialysis treatment 3 times per week (with about 4 hours per dialysis)
  • Chronic (i.e. repeated) paroxysmal, persistent or permanent non-valvular atrial fibrillation (NVAF) 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 atrial flutter 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 that require chronic anticoagulation (e.g., a prosthetic mechanical heart valve).
  • Active infective endocarditis
  • Any planned interventional or surgical AF or atrial flutter 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
  • 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 NVAF
  • 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).
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sabine Jürgensmeyer, Dr.0049 (0) 251 980 ext 1346[email protected]
Contact: Emilia Czarnecki0049 (0) 251 980 ext 1340[email protected]
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02933697
Other Study ID Numbers  ICMJE AXADIA - AFNET 8
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Atrial Fibrillation Network
Study Sponsor  ICMJE Atrial Fibrillation Network
Collaborators  ICMJE
  • Bristol-Myers Squibb
  • Pfizer
Investigators  ICMJE
Principal Investigator:Holger Reinecke, Prof. Dr.Universitätsklinikum Münster
PRS Account Atrial Fibrillation Network
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP