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Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation : Study protocol for a registry-based randomised controlled trial

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo LU ; Terént, Andreas; Öhagen, Patrik and Oldgren, Jonas (2017) In Trials 18(1).
Abstract

Background: Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. Methods/Design: The TIMING study is a... (More)

Background: Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. Methods/Design: The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. Conclusion: The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. Trial registration: ClinicalTrials.gov, NCT02961348. Registered on 8 November 2016.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute ischemic stroke, Atrial fibrillation, Oral anticoagulation, Randomised clinical trial
in
Trials
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85036513356
  • wos:000417073600004
ISSN
1745-6215
DOI
10.1186/s13063-017-2313-9
language
English
LU publication?
yes
id
b5e67e29-f0ec-4c74-8f33-989f2d9bffb7
date added to LUP
2017-12-18 08:58:27
date last changed
2018-01-16 13:28:00
@article{b5e67e29-f0ec-4c74-8f33-989f2d9bffb7,
  abstract     = {<p>Background: Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. Methods/Design: The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. Conclusion: The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. Trial registration: ClinicalTrials.gov, NCT02961348. Registered on 8 November 2016.</p>},
  articleno    = {581},
  author       = {Åsberg, Signild and Hijazi, Ziad and Norrving, Bo and Terént, Andreas and Öhagen, Patrik and Oldgren, Jonas},
  issn         = {1745-6215},
  keyword      = {Acute ischemic stroke,Atrial fibrillation,Oral anticoagulation,Randomised clinical trial},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Trials},
  title        = {Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation : Study protocol for a registry-based randomised controlled trial},
  url          = {http://dx.doi.org/10.1186/s13063-017-2313-9},
  volume       = {18},
  year         = {2017},
}