Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a parallel, randomised, open-label, multicentre, prospective study

Xiaowen Hou, Xiaoqiu Li, Xinhong Wang, Huisheng Chen, Xiaowen Hou, Xiaoqiu Li, Xinhong Wang, Huisheng Chen

Abstract

Background: A recent study shows that dual antiplatelet therapy with clopidogrel plus aspirin is superior to aspirin monotherapy for minor stroke, which is defined as a National Institutes of Health Stroke Scale (NIHSS)score of ≤3. However, acute mild-moderate ischaemic stroke (4≤NIHSS≤10) still needs aggressive antiplatelet intervention to prevent deterioration and recurrence of stroke. The efficacy and safety of dual antiplatelet therapy versus aspirin monotherapy in the population are not clear. A multicentre clinical trial is designed to evaluate the efficacy and safety of clopidogrel plus aspirin therapy versus aspirin monotherapy within 48 hours of symptom onset of mild-moderate ischaemic stroke.

Methods/design: The study is a randomised, open-label, multicentre, prospective trial with a target enrolment of 2700 patients from 60 centres in Northeast China. A treatment allocation identification number to each enrolled patient will be provided by a random number generator. The follow-up time for the clopidogrel plus aspirin and aspirin monotherapy groups is 90 days. The primary efficacy endpoint is a stroke progression event, which is defined as ≥4 point increase in the NIHSS score in 48 hours. The second efficacy endpoints include new ischaemic stroke within 90 days, change in the NIHSS score within 14 days, modified Rankin Scale score on day 90 and other vascular or death events within 90 days. The safety endpoints include mucocutaneous haemorrhage, organ haemorrhage and intracranial haemorrhage, adverse events and severe adverse events. χ2 test, t-test (or Mann-Whitney test), survival analysis and Cox proportional hazards models will be conducted. The findings of the study may provide an important evidence for clinical practice for these patients.

Discussion: The trial will be conducted under a rational design and will provide valuable evidence on the appropriate treatment for this population.

Ethics and dissemination: The study was reviewed and approved by the Ethics Committee of the General Hospital of Shen-Yang Military Region (no K(2016) 6).

Trial registration number: NCT02869009; Pre-results.

Keywords: antiplatelet therapy; aspirin; clopidogrel plus aspirin; stroke.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flow diagram of the study. mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale.

References

    1. Wardlaw JM, Zoppo G, Yamaguchi T. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2003;3:CD000213 10.1002/14651858.CD000213
    1. Sandercock P, Gubitz G, Foley P, et al. . Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2003;2:CD000029 10.1002/14651858.CD000029
    1. Hacke W, Kaste M, Bluhmki E, et al. . Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317–29. 10.1056/NEJMoa0804656
    1. Lu X, Huang Y. Thrombolysis treatment of acute ischemic stroke. Chin J Geriatr Heart Brain Vessel [Chinese] 2014;16:1230–2.
    1. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997;349:1569–81. 10.1016/S0140-6736(97)04011-7
    1. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997;349:1641–9.
    1. Powers WJ, Rabinstein AA, Ackerson T, et al. . 2018 guidelines for the early management of patients with acute ischemic stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2018;49:e46–e99. 10.1161/STR.0000000000000158
    1. Neurology branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of acute ischemic stroke in China 2014. Chin J Neurol [Chinese] 2015;48:246–57.
    1. Wong KS, Chen C, Fu J, et al. . Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial. Lancet Neurol 2010;9:489–97. 10.1016/S1474-4422(10)70060-0
    1. Li Z, Wang Y, Zhao X, et al. . Treatment effect of clopidogrel plus aspirin within 12 hours of acute minor stroke or transient ischemic attack. J Am Heart Assoc 2016;5:e003038 10.1161/JAHA.115.003038
    1. Keller TT, Squizzato A, Middeldorp S. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database Syst Rev 2007;3:CD005158 10.1002/14651858.CD005158.pub2
    1. Wang Y, Wang Y, Zhao X, et al. . Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369:11–19. 10.1056/NEJMoa1215340
    1. Johnston SC, Easton JD, Farrant M, et al. . Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018;379:215–25. 10.1056/NEJMoa1800410
    1. Kernan WN, Ovbiagele B, Black HR, et al. . Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160–236. 10.1161/STR.0000000000000024
    1. Ge F, Lin H, Liu Y, et al. . Dual antiplatelet therapy after stroke or transient ischaemic attack - how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis. Eur J Neurol 2016;23:1051–7. 10.1111/ene.12982
    1. Wang Z, Xu C, Wang P, et al. . Combined clopidogrel-aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds. Neurol Res 2015;37:993–7. 10.1179/1743132815Y.0000000087
    1. Wasserman JK, Perry JJ, Sivilotti ML, et al. . Computed tomography identifies patients at high risk for stroke after transient ischemic attack/nondisabling stroke: prospective, multicenter cohort study. Stroke 2015;46:114–9. 10.1161/STROKEAHA.114.006768
    1. Kennedy J, Hill MD, Ryckborst KJ, et al. . Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 2007;6:961–9. 10.1016/S1474-4422(07)70250-8
    1. He F, Xia C, Zhang JH, et al. . Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke. J Clin Neurosci 2015;22:83–6. 10.1016/j.jocn.2014.05.038
    1. von Kummer R, Broderick JP, Campbell BC, et al. . The heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke 2015;46:2981–6. 10.1161/STROKEAHA.115.010049
    1. Hu LP. The application of statistical tri-type theory in trial design. Beijing: People’s military medical publisher, 2006.
    1. Johnston SC, Amarenco P, Albers GW, et al. . Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 2016;375:35–43. 10.1056/NEJMoa1603060
    1. Gorelick PB, Wong KS, Bae HJ, et al. . Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier. Stroke 2008;39:2396–9. 10.1161/STROKEAHA.107.505776
    1. Wong LK. Global burden of intracranial atherosclerosis. Int J Stroke 2006;1:158–9. 10.1111/j.1747-4949.2006.00045.x
    1. Pan Y, Jing J, Chen W, et al. . Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE. Neurology 2017;88:1906–11. 10.1212/WNL.0000000000003941
    1. Sacco RL, Kasner SE, Broderick JP, et al. . An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:2064–89. 10.1161/STR.0b013e318296aeca

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