Dabigatran Following Transient Ischemic Attack and Minor Stroke

Summary

Rationale: To date, anticoagulant therapy in acute stroke has also been limited by excess hemorrhagic events. The oral anticoagulant dabigatran is a novel agent, which has been shown to be associated with much lower intracranial hemorrhage rates. It has been suggested that this agent may provide the superior benefits of anticoagulation in acute stroke, without the concomitant increase in hemorrhage risk associated with heparin/LMWH or warfarin. Study Design: DATAS II is a randomized, open label blinded endpoint trial. Participants (n=300) with TIA or ischemic stroke (NIHSS score \<9) will be enrolled within 48 hours of symptom onset from approximately four (4) health care centres across Canada. All participants will have an MRI with DWI lesion volume \< 25 ml. Participants will be randomized 1:1 to treatment with dabigatran for 30 days or ASA 81 mg daily (current standard of care). All stroke patients will initially be screened with a non-contrast CT scan of the brain. The first MRI will be performed within 48 hours of symptom onset. Imaging studies will be repeated at day 30. All patients will be assessed clinically at Day 30 and Day 90. Study Aims: 1. Establish the safety of early anticoagulation with the novel oral anticoagulant dabigatran in acute cerebrovascular syndrome patients. 2. Identify the rate of both symptomatic and asymptomatic hemorrhagic transformation (HT) associated with these treatments. 3. Identify predictors of HT associated with acute dabigatran treatment. Hypothesis: The Investigators hypothesize that symptomatic HT rates in dabigatran and ASA treated patients will not be significantly different. Study outcomes: The primary outcome is the rate of symptomatic hemorrhagic transformation (HT), defined as a parenchymal hematoma, which is \>30% of the infarcted area on DWI, with substantial space- occupying effect, associated with clinical worsening (≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score) within 5 weeks of treatment initiation. The major secondary outcome the rate of asymtomatic HT see on day 30 MRI sequence.

Timeline

Start

2015-01

Primary completion

2018-12-18

Completion

2018-12-18

Publications

• Cimen E, Ng K, Buck BH, Field T, Coutts SB, Gioia LC, Hill MD, Miller J, Benavente OR, Sharma M, Butcher K. Importance of infarct topography in determination of stroke mechanism and recurrence risk: a post-hoc analysis of the dabigatran acute treatment of stroke trial. BMJ Open. 2025 Jan 9;15(1):e087704. doi: 10.1136/bmjopen-2024-087704.
• Alrohimi A, Rose DZ, Burgin WS, Renati S, Hilker NC, Deng W, Oliveira GH, Beckie TM, Labovitz AJ, Fradley MG, Tran N, Gioia LC, Kate M, Ng K, Dowlatshahi D, Field TS, Coutts SB, Siddiqui M, Hill MD, Miller J, Jickling G, Shuaib A, Buck B, Sharma M, Butcher KS. Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials. Int J Stroke. 2023 Aug;18(7):864-872. doi: 10.1177/17474930231164891. Epub 2023 Mar 26.
• Butcher KS, Ng K, Sheridan P, Field TS, Coutts SB, Siddiqui M, Gioia LC, Buck B, Hill MD, Miller J, Klahr AC, Sivakumar L, Benavente OR, Hart RG, Sharma M. Dabigatran Treatment of Acute Noncardioembolic Ischemic Stroke. Stroke. 2020 Apr;51(4):1190-1198. doi: 10.1161/STROKEAHA.119.027569. Epub 2020 Feb 26.
• Ng KH, Sharma M, Benavente O, Gioia L, Field TS, Hill MD, Coutts SB, Butcher K; DATAS-2 Investigators. Dabigatran following acute transient ischemic attack and minor stroke II (DATAS II). Int J Stroke. 2017 Oct;12(8):910-914. doi: 10.1177/1747493017711947. Epub 2017 Jun 6.

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Indications