Cerebral HemorrhagePhase 2APACHE-AFNCT02565693
Apixaban After Anticoagulation-associated Intracerebral Haemorrhage in Patients With Atrial Fibrillation
A Phase 2 study testing Apixaban, Aspirin and Carbasalate calcium in people with Cerebral Hemorrhage and Atrial Fibrillation, run by UMC Utrecht at 16 sites in Netherlands.
Trial summary
There is a marked lack of evidence on the optimal prevention of ischaemic stroke in patients with atrial fibrillation and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Hemorrhage, Atrial Fibrillation
- What is being tested?
- Apixaban, Aspirin and Carbasalate calcium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 16 sitesNetherlands
- Study dates
- Sep 2014to 31 Jan 2021
- Phase
- Phase 2
- 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
- Intracerebral haemorrhage (including including isolated spontaneous intraventricular haemorrhage), documented with CT or MRI, during treatment with anticoagulation (VKA, any direct thrombin inhibitor, any factor Xa inhibitor, or (low molecular weight) heparin at a therapeutic dose).
- The haemorrhage has occurred between 7 and 90 days before randomization.
- Diagnosis of (paroxysmal) non-valvular AF, documented on electrocardiography.
- A CHA2DS2-VASc score ≥ 2.
- Score on the modified Rankin scale (mRS)≤4.
- Equipoise regarding the optimal medical treatment for the prevention of stroke.
- Age ≥ 18 years.
- Written informed consent by the patient or by a legal representative
Who cannot join
- Conditions other than atrial fibrillation for which the patient requires long-term anticoagulation
- A different clinical indication for the use of an antiplatelet drug even if treated with apixaban, such as clopidogrel for recent coronary stenting.
- Mechanical prosthetic heart valve (biological prosthetic heart valves are allowed) or rheumatic mitral valve disease.
- Serious bleeding event in the previous 6 months, except for intracerebral haemorrhage.
- High risk of bleeding (e.g., active peptic ulcer disease, a platelet count of <100,000.mL-1 or haemoglobin level of <6.2 mMol.L-1, ischaemic stroke in the previous 7 days (patients are eligible thereafter), documented haemorrhagic tendencies, or blood dyscrasias).
- Current alcohol or drug abuse.
Show all 13Show fewer
- Life expectancy of less than 1 year.
- Severe renal insufficiency (a serum creatinine level of more than 221 μmol per liter or a calculated creatinine clearance of <15 ml per minute).
- Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range or a total bilirubin more than 1.5 times the upper limit of the normal range, unless a benign causative factor (e.g. Gilbert's syndrome) is known or identified.
- Allergy to apixaban.
- Use of strong cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors (e.g. systemic azole-antimycotics as ketoconazole or HIV protease inhibitors such as ritonavir).
- Pregnancy or breastfeeding.
- Women of childbearing potential: any woman who has begun menstruation and is not postmenopausal or otherwise permanently unable to conceive. A postmenopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Netherlands16 sites
Amsterdam UMC
Amsterdam
OLVG
Amsterdam
Gelre Ziekenhuizen
Apeldoorn
Rijnstate
Arnhem
Amphia Ziekenhuis
Breda
Albert Schweitzer Ziekenhuis
Dordrecht
Medisch Spectrum Twente
Enschede
University Medical Center Groningen
Groningen
Zuyderland Ziekenhuis
Heerlen
Leiden University Medical Center
Leiden
Maastricht University Medical Center
Maastricht
Radboud University Medical Center
Nijmegen
Erasmus MC
Rotterdam
Haaglanden MC
The Hague
Elisabeth-Tweesteden Ziekenhuis
Tilburg
UMC Utrecht
Utrecht, 3584CX
About this study
Official title: Apixaban Versus Antiplatelet Drugs or no Antithrombotic Drugs After Anticoagulation-associated Intracerebral Haemorrhage in Patients With Atrial Fibrillation: A Randomised Phase II Clinical Trial
There is a marked lack of evidence on the optimal prevention of ischaemic stroke in patients with atrial fibrillation and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. These patients are currently treated with vitamin K antagonists, DOACs, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Treatment with a direct oral anticoagulant like apixaban might be an attractive alternative in terms of a low risk of recurrent ICH, while at the same time being effective for the prevention of ischaemic stroke. This study aims to obtain reliable estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage who are treated with apixaban versus those who are treated with antiplatelet drugs or no antithrombotic drug at all.
This study has a multi-centre, phase II, randomised, open-label clinical trial with blinded outcome assessment design.
Read the detailed description
Rationale: There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thrombo-embolic events in patients with non-valvular atrial fibrillation (AF) and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. These patients are currently treated with oral anticoagulants, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Randomised trials in patients with AF but without ICH have convincingly shown that vitamin K antagonists (VKAs, such as warfarin) reduce the risk of ischaemic stroke and other thrombo-embolic events, but increase the risk of bleeding as compared to no anticoagulant therapy. In the ARISTOTLE trial, the direct oral anticoagulant (DOAC) apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. In other trials, the other DOACs, rivaroxaban, edoxaban, and dabigatran had a similar benefit as compared with warfarin. DOACs have not been tested in patients with AF and a recent ICH. Apixaban is the only DOAC tested against aspirin in a large randomised trial, in which patients with AF who were treated with apixaban had a lower risk of stroke or systemic embolism than those treated with aspirin, whereas ICH rates were similar in both treatment groups. We hypothesize that in patients with AF who survived an anticoagulation-associated ICH, apixaban is an attractive alternative to antiplatelet drugs or no antithrombotic treatment at all in terms of a low risk of recurrent ICH, while at the same time being more effective for the prevention of ischaemic stroke.
Objective: 1) To obtain reliable estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage who are treated with apixaban versus those who are treated with an antiplatelet drug or no antithrombotic drugs. 2) To compare the rates of all-cause death, stroke, ischaemic stroke, ICH, other major haemorrhage, systemic embolism, and functional outcome between patients treated with apixaban and those who are treated with an antiplatelet drug or no antithrombotic drugs.
Study design: A randomised, open, multi-center clinical trial with masked outcome assessment.
Study population: 100 adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention therapy.
Intervention: Apixaban 5 mg twice daily versus antiplatelet therapy or no antithrombotic drugs.
Primary outcome: Vascular death or non-fatal stroke during follow-up. Time frame: We aim to include 100 patients in six years. All patients will be followed up for the duration of the study, but at least for six months.
- Conditions
- Cerebral Hemorrhage, Atrial Fibrillation
- Being tested
- Apixaban, Aspirin, Carbasalate calcium, Clopidogrel, Dipyridamole
- Medical subject headings
- Cerebral Hemorrhage, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
AspirinDrug
Also called Acetylsalicylic acid
Carbasalate calciumDrug
ClopidogrelDrug
DipyridamoleDrug
No antithrombotic treatmentOther
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Experimental | Apixaban: oral, 5 mg twice daily. If two of the three following criteria are met, the dose will be reduced to 2.5 mg twice daily:
* Age ≥ 80 years
* Body weight ≤ 60 kg
* Serum creatinine ≥ 133 μmol. Additionally, if the creatinin clearance is below 30 ml per minute, the dose will be reduced to 2.5 mg twice daily. Receives: Drug: Apixaban |
| Avoiding oral anticoagulants | Other | The following treatment regimens are allowed in the comparator arm:
- No antithrombotic treatment
or:
* Acetylsalicylic acid 80 mg once daily
* Carbasalate calcium 100 mg once daily
* Clopidogrel 75 mg once daily
* Acetylsalicylic acid 80 mg once daily and dipyridamole 200 mg twice daily
* Carbasalate calcium 100 mg once daily and dipyridamole 200 mg twice daily Receives: Drug: Aspirin; Drug: Carbasalate calcium; Drug: Clopidogrel; Drug: Dipyridamole; Other: No antithrombotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who experience the combination of vascular death or non-fatal stroke (cerebral infarction, intracerebral haemorrhage, or subarachnoid haemorrhage)
Ischaemic stroke Clinical evidence of the sudden onset of an new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without evidence of a intracerebral haemorrhage on a CT or MRI scan or at post-mortem investigation.
Intracerebral haemorrhage Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, with a corresponding intracerebral haemorrhage on a CT or MR scan or at post-mortem investigation.
Unclassified stroke Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without imaging or post-mortem investigations performed.
Subarachnoid haemorrhage Subarachnoid haemorrhage (SAH) demonstrated by CT, lumbar puncture, or at post-mortem investigation.
Vascular death See Outcome 2, Vascular death
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Secondary outcomes (10)
Number of patients who experience vascular death
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience death from any cause.
Vascular death Death from cerebral infarction; intracerebral, subarachnoid, epidural, or subdural haemorrhage; unclassified stroke; myocardial infarction; extracranial haemorrhage; or systemic embolism. Death should have been unlikely without the events mentioned above. Other events classifying as vascular death: fatal arterial or gastric bleeding, terminal heart failure, fatal pulmonary embolism, and sudden death, defined as death within one hour after onset of symptoms.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience all stroke.
Ischaemic stroke Clinical evidence of the sudden onset of an new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without evidence of a intracerebral haemorrhage on a CT or MRI scan or at post-mortem investigation.
Intracerebral haemorrhage Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, with a corresponding intracerebral haemorrhage on a CT or MR scan or at post-mortem investigation.
Unclassified stroke Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without imaging or post-mortem investigations performed.
Subarachnoid haemorrhage Subarachnoid haemorrhage (SAH) demonstrated by CT, lumbar puncture, or at post-mortem investigation.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience ischaemic stroke.
Clinical evidence of the sudden onset of an new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without evidence of a intracerebral haemorrhage on a CT or MRI scan or at post-mortem investigation.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience intracerebral haemorrhage.
Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, with a corresponding intracerebral haemorrhage on a CT or MR scan or at post-mortem investigation.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience other major extracranial haemorrhage
Major extracranial bleeding will be defined using the ISTH criteria.55 1) Fatal bleeding, and/or 2) Symptomatic bleeding in a critical area or organ, such as intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or 3) Bleeding causing a fall in haemoglobin level of 1.24 mmol L-1 or more, or leading to transfusion of two or more units of whole blood or red cells.

Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience any intracranial haemorrhage other than ICH.
subdural haemorrhage: evidence of a subdural haematoma on a CT or MRI scan or at post-mortem investigations; epidural hematoma: evidence of an epidural haematoma on a CT or MRI scan or at post-mortem investigations.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience systemic embolism.
The diagnosis of systemic embolism requires a clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries) supported by evidence of embolism from surgical specimens, post-mortem investigations, angiography, vascular imaging, or other objective testing.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience myocardial infarction.
Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin] with at least 1 value above the 99th percentile upper reference limit and with at least 1 of the following:
Symptoms of ischemia. New or presumed new significant ST-segment-T wave changes or new left bundle branch block. Development of pathological Q waves in the ECG. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Identification of intracoronary thrombus by angiography or autopsy.
Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes or new LBBB, but death occurred before cardiac biomarkers were obtained, or before cardiac biomarker values would be increased.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience who experience a good functional outcome as assessed with the score on the modified Rankin Scale
Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988 May;19(5):604-7.
Measured: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study startSep 2014
- Primary completion31 Jan 2021
- Study completion31 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cerebral HemorrhageStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Heart Foundation, ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, H. Bart van der Worp, UMC Utrecht
- Investigators
- Catharina JM Klijn, MD PhD, Study chair, Radboud University Medical CenterH Bart van der Worp, MD PhD, Study chair, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565693
- Sponsor's protocol ID
- NL47761.041.14
- Other IDs
- 2014-000112-33, NTR4526, U1111-1154-5474, 2014
- Acronym
- APACHE-AF
- Status last verified
- Apr 2021
- First submitted
- 27 Aug 2015
- Last updated
- 14 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.
PubMed 36700520Schreuder FHBM, van Nieuwenhuizen KM, Hofmeijer J, Vermeer SE, Kerkhoff H, Zock E, Luijckx GJ, Messchendorp GP, van Tuijl J, Bienfait HP, Booij SJ, van den Wijngaard IR, Remmers MJM, Schreuder AHCML, Dippel DW, Staals J, Brouwers PJAM, Wermer MJH, Coutinho JM, Kwa VIH, van Gelder IC, Schutgens REG, Zweedijk B, Algra A, van Dalen JW, Jaap Kappelle L, Rinkel GJE, van der Worp HB, Klijn CJM; APACHE-AF Trial Investigators. Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial. Lancet Neurol. 2021 Nov;20(11):907-916. doi: 10.1016/S1474-4422(21)00298-2.
PubMed 34687635Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.
PubMed 34022170
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apixaban Versus Antiplatelet Drugs or no Antithrombotic Drugs After Anticoagulation-associated Intracerebral Haemorrhage in Patients With Atrial Fibrillation: A Randomised Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT02565693
- Acronym / sponsor ID
- APACHE-AF / NL47761.041.14
- Conditions
- Cerebral Hemorrhage, Atrial Fibrillation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Dutch Heart Foundation, ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Sep 2014 (actual)
- Primary completion
- 31 Jan 2021 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 1 Oct 2015 (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.
There is a marked lack of evidence on the optimal prevention of ischaemic stroke in patients with atrial fibrillation and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. These patients are currently treated with vitamin K antagonists, DOACs, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Treatment with a direct oral anticoagulant like apixaban might be an attractive alternative in terms of a low risk of recurrent ICH, while at the same time being effective for the prevention of ischaemic stroke. This study aims to obtain reliable estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage who are treated with apixaban versus those who are treated with antiplatelet drugs or no antithrombotic drug at all.
This study has a multi-centre, phase II, randomised, open-label clinical trial with blinded outcome assessment design.
Detailed description
Rationale: There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thrombo-embolic events in patients with non-valvular atrial fibrillation (AF) and a recent intracerebral haemorrhage (ICH) during treatment with oral anticoagulation. These patients are currently treated with oral anticoagulants, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Randomised trials in patients with AF but without ICH have convincingly shown that vitamin K antagonists (VKAs, such as warfarin) reduce the risk of ischaemic stroke and other thrombo-embolic events, but increase the risk of bleeding as compared to no anticoagulant therapy. In the ARISTOTLE trial, the direct oral anticoagulant (DOAC) apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. In other trials, the other DOACs, rivaroxaban, edoxaban, and dabigatran had a similar benefit as compared with warfarin. DOACs have not been tested in patients with AF and a recent ICH. Apixaban is the only DOAC tested against aspirin in a large randomised trial, in which patients with AF who were treated with apixaban had a lower risk of stroke or systemic embolism than those treated with aspirin, whereas ICH rates were similar in both treatment groups. We hypothesize that in patients with AF who survived an anticoagulation-associated ICH, apixaban is an attractive alternative to antiplatelet drugs or no antithrombotic treatment at all in terms of a low risk of recurrent ICH, while at the same time being more effective for the prevention of ischaemic stroke.
Objective: 1) To obtain reliable estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage who are treated with apixaban versus those who are treated with an antiplatelet drug or no antithrombotic drugs. 2) To compare the rates of all-cause death, stroke, ischaemic stroke, ICH, other major haemorrhage, systemic embolism, and functional outcome between patients treated with apixaban and those who are treated with an antiplatelet drug or no antithrombotic drugs.
Study design: A randomised, open, multi-center clinical trial with masked outcome assessment.
Study population: 100 adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention therapy.
Intervention: Apixaban 5 mg twice daily versus antiplatelet therapy or no antithrombotic drugs.
Primary outcome: Vascular death or non-fatal stroke during follow-up. Time frame: We aim to include 100 patients in six years. All patients will be followed up for the duration of the study, but at least for six months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Experimental | Drug: ApixabanApixaban: oral, 5 mg twice daily. If two of the three following criteria are met, the dose will be reduced to 2.5 mg twice daily: * Age ≥ 80 years * Body weight ≤ 60 kg * Serum creatinine ≥ 133 μmol. Additionally, if the creatinin clearance is below 30 ml per minute, the dose will be reduced to 2.5 mg twice daily. |
| Avoiding oral anticoagulants | Other | Drug: Aspirin, Drug: Carbasalate calcium, Drug: Clopidogrel, Drug: Dipyridamole, Other: No antithrombotic treatmentThe following treatment regimens are allowed in the comparator arm: - No antithrombotic treatment or: * Acetylsalicylic acid 80 mg once daily * Carbasalate calcium 100 mg once daily * Clopidogrel 75 mg once daily * Acetylsalicylic acid 80 mg once daily and dipyridamole 200 mg twice daily * Carbasalate calcium 100 mg once daily and dipyridamole 200 mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Intracerebral haemorrhage (including including isolated spontaneous intraventricular haemorrhage), documented with CT or MRI, during treatment with anticoagulation (VKA, any direct thrombin inhibitor, any factor Xa inhibitor, or (low molecular weight) heparin at a therapeutic dose).
- The haemorrhage has occurred between 7 and 90 days before randomization.
- Diagnosis of (paroxysmal) non-valvular AF, documented on electrocardiography.
- A CHA2DS2-VASc score ≥ 2.
- Score on the modified Rankin scale (mRS)≤4.
Key exclusion criteria (13 listed)
- Conditions other than atrial fibrillation for which the patient requires long-term anticoagulation
- A different clinical indication for the use of an antiplatelet drug even if treated with apixaban, such as clopidogrel for recent coronary stenting.
- Mechanical prosthetic heart valve (biological prosthetic heart valves are allowed) or rheumatic mitral valve disease.
- Serious bleeding event in the previous 6 months, except for intracerebral haemorrhage.
- High risk of bleeding (e.g., active peptic ulcer disease, a platelet count of <100,000.mL-1 or haemoglobin level of <6.2 mMol.L-1, ischaemic stroke in the previous 7 days (patients are eligible thereafter), documented haemorrhagic tendencies, or blood dyscrasias).
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: Eliquis | Drug | Apixaban |
| AspirinAlso: Acetylsalicylic acid | Drug | Avoiding oral anticoagulants |
| Carbasalate calcium | Drug | Avoiding oral anticoagulants |
| Clopidogrel | Drug | Avoiding oral anticoagulants |
| Dipyridamole | Drug | Avoiding oral anticoagulants |
| No antithrombotic treatment | Other | Avoiding oral anticoagulants |
Primary outcome
Number of patients who experience the combination of vascular death or non-fatal stroke (cerebral infarction, intracerebral haemorrhage, or subarachnoid haemorrhage)
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Ischaemic stroke Clinical evidence of the sudden onset of an new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without evidence of a intracerebral haemorrhage on a CT or MRI scan or at post-mortem investigation. Intracerebral haemorrhage Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, with a corresponding intracerebral haemorrhage on a CT or MR scan or at post-mortem investigation. Unclassified stroke Clinical evidence of the sudden onset of a new neurological deficit, or an increase in an existing deficit, persisting for more than 24 hours, without imaging or post-mortem investigations performed. Subarachnoid haemorrhage Subarachnoid haemorrhage (SAH) demonstrated by CT, lumbar puncture, or at post-mortem investigation. Vascular death See Outcome 2, Vascular death
10 secondary outcomes
Number of patients who experience vascular death
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience death from any cause.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience all stroke.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience ischaemic stroke.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience intracerebral haemorrhage.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience other major extracranial haemorrhage
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience any intracranial haemorrhage other than ICH.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience systemic embolism.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience myocardial infarction.
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) months.
Number of patients who experience who experience a good functional outcome as assessed with the score on the modified Rankin Scale
Time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) 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 14 Apr 2021.
- Derived from this study: PubMed 36700520Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.
- Derived from this study: PubMed 34687635Schreuder FHBM, van Nieuwenhuizen KM, Hofmeijer J, Vermeer SE, Kerkhoff H, Zock E, Luijckx GJ, Messchendorp GP, van Tuijl J, Bienfait HP, Booij SJ, van den Wijngaard IR, Remmers MJM, Schreuder AHCML, Dippel DW, Staals J, Brouwers PJAM, Wermer MJH, Coutinho JM, Kwa VIH, van Gelder IC, Schutgens REG, Zweedijk B, Algra A, van Dalen JW, Jaap Kappelle L, Rinkel GJE, van der Worp HB, Klijn CJM; APACHE-AF Trial Investigators. Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial. Lancet Neurol. 2021 Nov;20(11):907-916. doi: 10.1016/S1474-4422(21)00298-2.
- Derived from this study: PubMed 34022170Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.
- Trial websiteLink provided by the sponsor.
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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.
Catharina JM Klijn, MD PhD study chair
Radboud University Medical Center
H Bart van der Worp, MD PhD study chair
UMC Utrecht
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apixaban, Aspirin and Carbasalate calcium in people with Cerebral Hemorrhage and Atrial Fibrillation, run by UMC Utrecht at 16 sites in Netherlands.
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 8 inclusion and 13 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 14 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Number of patients who experience the combination of vascular death or non-fatal stroke (cerebral infarction, intracerebral haemorrhage, or subarachnoid haemorrhage) (time frame: Throughout the study. Patients will be followed up between 12 (minimum) and 72 (maximum) 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 NCT02565693, which also lists 3 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 14 Apr 2021.