Rationale and design of a stepped wedge cluster randomised trial to improve acute reperfusion treatment quality for stroke: IMPROVE stroke care in China

Zixiao Li, Chunjuan Wang, Xinmiao Zhang, Lixia Zong, Hongyu Zhou, Hongqiu Gu, Yong Jiang, Yuesong Pan, Xia Meng, Qi Zhou, Haifen Zhao, Xin Yang, Meng Wang, Yunyun Xiong, Xingquan Zhao, Yilong Wang, Liping Liu, Xudong Ma, Louise Morgan, Ying Xian, Lee H Schwamm, Yongjun Wang, Zixiao Li, Chunjuan Wang, Xinmiao Zhang, Lixia Zong, Hongyu Zhou, Hongqiu Gu, Yong Jiang, Yuesong Pan, Xia Meng, Qi Zhou, Haifen Zhao, Xin Yang, Meng Wang, Yunyun Xiong, Xingquan Zhao, Yilong Wang, Liping Liu, Xudong Ma, Louise Morgan, Ying Xian, Lee H Schwamm, Yongjun Wang

Abstract

Background: Reperfusion therapy is the most effective treatment for acute ischaemic stroke (AIS) but remains underutilised in China. There is an urgent need to develop tailored strategies to increase adherence to intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) within the guideline-recommended time window for eligible patients.

Aims: This study aims to investigate the efficacy of a comprehensive quality improvement intervention on adherence to guideline-recommended reperfusion therapy for patients with AIS in China.

Design: The Improve Acute Reperfusion Treatment Quality for Stroke in China (IMPROVE Stroke Care in China) trial is designed as a stepped wedge cluster randomised trial within 51 hospitals. We developed the comprehensive intervention 'STEP' (Strategies, Toolkit, Exploration, Paradigm) to promote the reconstruction of workflow in stroke centres and shorten in-hospital delay of reperfusion treatment for patients with AIS. The participating hospitals (clusters) were randomised to three groups (cohorts) for different predefined steps to intervention implementation. The primary outcome was the adherent rate of IVT or EVT for eligible patients within the time window. The sample size was estimated to be 7644, and was determined by the number of cases to be enrolled in five study periods to detect a relative increase of 30% (from 19% to 25%) with 90% power and intraclass correlation coefficient of 0.03. All efficacy analyses will be conducted based on the intention-to-treat principle. The primary outcome will be analysed using a mixed-effects logistic regression with a random effect for the cluster (hospital), and a fixed effect for the strategy and period.

Conclusions: If the efficacy is well established, this targeted comprehensive intervention STEP will inform national strategies to increase adherence to guideline-recommended performance on reperfusion therapy.

Trial registration number: clinicaltrials.gov Identifier: NCT003578107.

Trial registration: ClinicalTrials.gov NCT03578107.

Keywords: clinical trial; stroke.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
The flow chart of the IMPROVE trial. IMPROVE, Improve Acute Reperfusion Treatment Quality for Stroke in China

References

    1. GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet 2020;396:1204–22. 10.1016/S0140-6736(20)30925-9
    1. Campbell BCV, Khatri P. Stroke. Lancet 2020;396:129–42. 10.1016/S0140-6736(20)31179-X
    1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–8. 10.1056/NEJM199512143332401
    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. Berkhemer OA, Fransen PSS, Beumer D, et al. . A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11–20. 10.1056/NEJMoa1411587
    1. Campbell BCV, Mitchell PJ, Kleinig TJ, et al. . Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009–18. 10.1056/NEJMoa1414792
    1. Goyal M, Demchuk AM, Menon BK, et al. . Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019–30. 10.1056/NEJMoa1414905
    1. Jovin TG, Chamorro A, Cobo E, et al. . Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296–306. 10.1056/NEJMoa1503780
    1. Saver JL, Goyal M, Bonafe A, et al. . Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285–95. 10.1056/NEJMoa1415061
    1. Powers WJ, Rabinstein AA, Ackerson T. 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;2018:e46–110. 10.1161/STR.0000000000000158
    1. Association CS . 2018 guideline for endovascular treatment in acute ischemic stroke patients. Chin J Stroke 2018;2018:706–29.
    1. Li Z, Wang C, Zhao X, et al. . Substantial progress yet significant opportunity for improvement in stroke care in China. Stroke 2016;47:2843–9. 10.1161/STROKEAHA.116.014143
    1. Schwamm LH, Fonarow GC, Reeves MJ, et al. . Get with the Guidelines–Stroke is associated with sustained improvement in care for patients hospitalized with acute stroke or transient ischemic attack. Circulation 2009;119:107–15. 10.1161/CIRCULATIONAHA.108.783688
    1. Wang Y, Li Z, Wang Y, et al. . Chinese stroke center alliance: a national effort to improve healthcare quality for acute stroke and transient ischaemic attack: rationale, design and preliminary findings. Stroke Vasc Neurol 2018;3:256–62. 10.1136/svn-2018-000154
    1. Fonarow GC, Zhao X, Smith EE, et al. . Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA 2014;311:1632–40. 10.1001/jama.2014.3203
    1. Hemming K, Haines TP, Chilton PJ, et al. . The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting. BMJ 2015;350:h391. 10.1136/bmj.h391
    1. Wang Y, Jing J, Meng X, et al. . The third China national stroke registry (CNSR-III) for patients with acute ischaemic stroke or transient ischaemic attack: design, rationale and baseline patient characteristics. Stroke and Vascular Neurology 2019;4:158–64. 10.1136/svn-2019-000242
    1. Adams HP, Bendixen BH, Kappelle LJ, et al. . Classification of subtype of acute ischemic stroke. definitions for use in a multicenter clinical trial. TOAST. trial of ORG 10172 in acute stroke treatment. Stroke 1993;24:35–41. 10.1161/01.STR.24.1.35
    1. Jo B, Asparouhov T, Muthén BO. Intention-To-Treat analysis in cluster randomized trials with noncompliance. Stat Med 2008;27:5565–77. 10.1002/sim.3370
    1. Ma H, Campbell BCV, Parsons MW, et al. . Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med 2019;380:1795–803. 10.1056/NEJMoa1813046
    1. Campbell BCV, Ma H, Ringleb PA, et al. . Extending thrombolysis to 4·5–9 H and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. The Lancet 2019;394:139–47. 10.1016/S0140-6736(19)31053-0
    1. Nogueira RG, Jadhav AP, Haussen DC, et al. . Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378:11–21. 10.1056/NEJMoa1706442
    1. Albers GW, Marks MP, Kemp S, et al. . Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018;378:708–18. 10.1056/NEJMoa1713973
    1. Yang P, Zhang Y, Zhang L, et al. . Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med 2020;382:1981–93. 10.1056/NEJMoa2001123
    1. Zi W, Qiu Z, Li F, et al. . Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke. JAMA 2021;325:234–43. 10.1001/jama.2020.23523
    1. Lees KR, Bluhmki E, von Kummer R, et al. . Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, atlantis, NINDS, and epithet trials. The Lancet 2010;375:1695–703. 10.1016/S0140-6736(10)60491-6
    1. Pan Y, Zhang L, Li Z, et al. . Cost-Effectiveness of a multifaceted quality improvement intervention for acute ischemic stroke in China. Stroke 2020;51:1265–71. 10.1161/STROKEAHA.119.027980

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