AXADIA – AFNET 8 is an investigator‐driven, prospective, parallel‐group, national, multicenter, phase IIIb trial.
The primary outcome is to 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.
The secondary outcome is to 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.
Furthermore a pharmacokinetic sub-study will be performed with a small number of patients (n=28) in the apixaban treatment group in order to investigate/ determine plasma levels of apixaban prior and after hemodialysis.
The trial will be performed/ conducted in about 40 sites in Germany with 222 patients.
Patients are eligible for AXADIA, if they meet following 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)
• Increased risk of stroke or systemic embolism identified by a CHA2DS2-VASc score ≥ 2 an indication for oral anticoagulation
The study participants will be randomized to either receiving apixaban or phenprocoumon (1:1).
Patients with chronic kidney disease (CKD) suffer from a high cardiovascular morbidity and mortality. Moreover, their number is dramatically increasing. This is due to several causes, especially to the increasing prevalence of diabetes, hypertension, and in general a higher number of elderly people.
Although about 6 million people suffer from CKD in Germany, only 120,000 are alive in CKD stage 4 and 85,000 in stage 5 (=end-stage kidney disease (ESKD) on peritoneal or hemodialysis). The reason for this phenomenon is the deleterious mortality in the advanced CKD stages 4 and 5.
In contrast, only little attention has yet been paid to the problem of atrial fibrillation (AF) in patients with CKD, although this arrhythmia is very frequent in this cohort due to the high prevalence of structural heart disease and hypertension as the major risk factors.
Patients with CKD suffer from a high risk of both thromboembolic events and bleedings. Concordantly, ischemic (and hemorrhagic) stroke is a typical and frequent complication in ESKD. So far, there is no evidence-based treatment for patients with ESKD on hemodialysis and thus, there is a need for anticoagulation especially for these high morbid patients.
Apixaban is a novel, potent, oral anticoagulans, belonging to the group of non-vitamin-K anticoagulants, with a low renal clearance (<30% of total clearance). Therefore, apixaban may offer a safe and effective alternative to VKA for this special patient collective.
Thus, the primary goal of the present AXADIA trial 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 AXADIA 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.
AXADIA is an investigator‐driven, prospective, parallel‐group, national, 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.
Participating country and head of trial
Co-ordinating Investigator Cardiology/ Head of the Trial
Prof. Dr. Holger Reinecke
Co-ordinating Investigator Nephrology/ Chief Investigator
Prof. Dr. Christoph Wanner
Scinetific committee – Steering Committee:
Prof. Dr. Paulus Kirchhof | Birmingham, UK
Prof. Dr. Holger Reinecke | Münster, Germany
Prof. Dr. Christoph Wanner | Würzburg, Germany
Prof. Dr. Johann Bauersachs | Hannover, Germany
Prof. Dr. Dr. Günter Breithardt | Münster, Germany
Dr. Joachim Gerß | Münster, Germany
Dr. Martin Sommer (nicht stimmberechtigtes Mitglied) | München, Germany
Dr. Michael Krekler (nicht stimmberechtigtes Mitglied) | München, Germany
As a physician you may – if qualified accordingly – participate in the AXADIA trial (Flyer in German).
If you are interested in recruiting patients for this trial in Germany, please contact the AFNET network office.