Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial.
BACKGROUND
There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage 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. Compared with warfarin, the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism, intracranial haemorrhage, and case fatality in patients with atrial fibrillation. Compared with aspirin, apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation, and has a similar risk of intracerebral haemorrhage. Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage. To inform a phase III trial, the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided.


METHODS
APACHE-AF is a phase II, multicentre, open-label, parallel-group, randomised clinical trial with masked outcome assessment. One hundred 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 strategy will be enrolled in 14 hospitals in The Netherlands. These patients will be randomly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation. Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician. The primary outcome is the composite of vascular death or non-fatal stroke during follow-up. We aim to include 100 patients in 2.5 years. All patients will be followed-up for the duration of the study, but at least for 1 year. Recruitment commenced in September 2014 and is ongoing. This trial is funded by the Dutch Heart Foundation (2012 T077) and ZonMW (015008048).


BACKGROUND
NTR4526 (16 April 2014).
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. k.m.vannieuwenhuizen-3@umcutrecht.nl.
Koen M
KM
van Nieuwenhuizen
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. h.b.vanderworp@umcutrecht.nl.
H Bart
HB
van der Worp
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. a.algra@umcutrecht.nl.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, STR. 7.140, PO Box 85500, 3508, GA, Utrecht, The Netherlands. a.algra@umcutrecht.nl.
Ale
A
Algra
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. l.j.kappelle@umcutrecht.nl.
L Jaap
LJ
Kappelle
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. g.j.e.rinkel@umcutrecht.nl.
Gabriel J E
GJ
Rinkel
Department of Cardiology, University Medical Center Groningen, PO Box 30.001, 9700, RB, Groningen, The Netherlands. i.c.van.gelder@umcg.nl.
Isabelle C
IC
van Gelder
Van Creveldkliniek, University Medical Center Utrecht, C01.425, PO Box 85500, 3508, GA, Utrecht, The Netherlands. r.schutgens@umcutrecht.nl.
Roger E G
RE
Schutgens
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, G03.232, PO Box 85500, 3508, GA, Utrecht, The Netherlands. karin.klijn@radboudumc.nl.|Department of Neurology, Radboud University Medical Center, PO Box 9101, 6500, HB, Nijmegen, The Netherlands. karin.klijn@radboudumc.nl.
Catharina J M
CJ
Klijn
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002543:Cerebral Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002985:Clinical Protocols; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009426:Netherlands; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban