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

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ClinicalTrials.gov Identifier: NCT02933697
Recruitment Status : Recruiting
First Posted : October 14, 2016
Last Update Posted : August 1, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Pfizer
Information provided by (Responsible Party):
Atrial Fibrillation Network

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.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 222 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 : June 20, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : July 2022


Arm Intervention/treatment
Active Comparator: Apixaban
2.5 mg apixaban twice daily for 6 to 24 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 Name: Elquis

Active Comparator: Vitamin-K antagonists (Phenprocoumon)
Phenprocoumon by INR (Target: 2.0-3.0) treatment for 6 to 24 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 Name: Marcumar




Primary Outcome Measures :
  1. 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: 6-24 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 :
  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 [ Time Frame: 6-24 months ]

Other Outcome Measures:
  1. Pharmacokinetic sub-study to determine plasma serum level [ Time Frame: 6-24 months ]
    A pharmacokinetic sub-study will be conducted with a small number of patients in the apixaban treatment group (n= 28) in order to determine plasma serum level of apixaban prior and after hemodialysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02933697


Contacts
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Contact: Sabine Jürgensmeyer, Dr. 0049 (0) 251 980 ext 1346 axadia@af-net.eu
Contact: Emilia Czarnecki 0049 (0) 251 980 ext 1340 emilia.czarnecki@af-net.eu

Locations
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Germany
Universitätsklinikum Münster Recruiting
Münster, Germany, 48149
Sponsors and Collaborators
Atrial Fibrillation Network
Bristol-Myers Squibb
Pfizer
Investigators
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Principal Investigator: Holger Reinecke, Prof. Dr. Universitätsklinikum Münster

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Atrial Fibrillation Network
ClinicalTrials.gov Identifier: NCT02933697     History of Changes
Other Study ID Numbers: AXADIA - AFNET 8
First Posted: October 14, 2016    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Atrial Fibrillation Network:
Atrial Fibrillation
Kidney disease
Anticoagulation

Additional relevant MeSH terms:
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Atrial Fibrillation
Kidney Diseases
Kidney Failure, Chronic
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Vitamins
Vitamin K
Apixaban
Phenprocoumon
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Antifibrinolytic Agents
Fibrin Modulating Agents
Hemostatics
Coagulants