Atrial FibrillationPhase 3AXADIANCT02933697
Compare Apixaban and Vitamin-K Antagonists in Patients With Atrial Fibrillation (AF) and End-Stage Kidney Disease (ESKD)
A Phase 3 study testing Apixaban and Phenprocoumon in people with Atrial Fibrillation and End-stage Kidney Disease, run by Atrial Fibrillation Network at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, End-stage Kidney Disease
- What is being tested?
- Apixaban and Phenprocoumon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteGermany
- Study dates
- 20 Jun 2017to 31 Jul 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Atrial Fibrillation, End-stage Kidney Disease
- Being tested
- Apixaban, Phenprocoumon
- Keywords
- Atrial Fibrillation, Kidney disease, Anticoagulation
- Medical subject headings
- Atrial Fibrillation, Kidney Failure, Chronic, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
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.
PhenprocoumonDrug
Also called Marcumar
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.
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Active comparator | 2.5 mg apixaban twice daily for 1 to 60 months Receives: Drug: Apixaban |
| Vitamin-K antagonists (Phenprocoumon) | Active comparator | Phenprocoumon by INR (Target: 2.0-3.0) treatment for 1 to 60 months Receives: Drug: Phenprocoumon |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
Measured: 1-60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study start20 Jun 2017
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atrial Fibrillation Network
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Pfizer
- Responsible party
- Sponsor
- Investigators
- Holger Reinecke, Prof. Dr., Principal investigator, Universitätsklinikum Münster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02933697
- Sponsor's protocol ID
- AXADIA - AFNET 8
- Acronym
- AXADIA
- Status last verified
- Sep 2022
- First submitted
- 7 Oct 2016
- Last updated
- 27 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36335915Reinecke 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.
PubMed 30206088
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02933697
- Acronym / sponsor ID
- AXADIA / AXADIA - AFNET 8
- Conditions
- Atrial Fibrillation, End-stage Kidney Disease
- Keywords
- Atrial Fibrillation, Kidney disease, Anticoagulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Atrial Fibrillation NetworkUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Pfizer
- Study start
- 20 Jun 2017 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Active comparator | Drug: Apixaban2.5 mg apixaban twice daily for 1 to 60 months |
| Vitamin-K antagonists (Phenprocoumon) | Active comparator | Drug: PhenprocoumonPhenprocoumon by INR (Target: 2.0-3.0) treatment for 1 to 60 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: EliquisPatients 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. | Drug | Apixaban |
| PhenprocoumonAlso: MarcumarSubjects 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. | Drug | Vitamin-K antagonists (Phenprocoumon) |
Primary outcome
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 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Derived from this study: PubMed 36335915Reinecke 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.
- Derived from this study: PubMed 30206088Reinecke 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Holger Reinecke, Prof. Dr. principal investigator
Universitätsklinikum Münster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban and Phenprocoumon in people with Atrial Fibrillation and End-stage Kidney Disease, run by Atrial Fibrillation Network at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02933697, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.