Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial (2024)

1. Jiejie Li, professor1,
2. Xia Meng, professor1,
3. Fu-Dong Shi, professor1,
4. Jing Jing, professor1,
5. Hong-Qiu Gu, professor1,
6. Aoming Jin, lecturer1,
7. Yong Jiang, professor1,
8. Hao Li, professor1,
9. S Claiborne Johnston, professor3,
10. Graeme J Hankey, professor4 5,
11. J Donald Easton, professor3,
12. Liguo Chang, professor6,
13. Penglai Shi, professor7,
14. Lihua Wang, professor8,
15. Xianbo Zhuang, professor9,
16. Haitao Li, professor10,
17. Yingzhuo Zang, professor11,
18. Jianling Zhang, professor12,
19. Zengqiang Sun, professor13,
20. Dongqi Liu, professor14,
21. Ying Li, professor15,
22. Hongqin Yang, professor16,
23. Jinguo Zhao, professor17,
24. Weiran Yu, lecturer1,
25. Anxin Wang, professor1,
26. Yuesong Pan, professor1,
27. Jinxi Lin, senior lecturer1,
28. Xuewei Xie, professor1,
29. Wei-Na Jin, professor1,
30. Shuya Li, professor1,
31. Siying Niu, lecturer1,
32. Yilong Wang, professor1,
33. Xingquan Zhao, professor1,
34. Zixiao Li, professor1,
35. Liping Liu, professor1,
36. Huaguang Zheng, professor1,
37. Yongjun Wang, professor1 2
38. on behalf of the CHANCE-3 Investigators

1. ¹Department of Neurology and China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
2. ²Clinical Center for Precision Medicine in Stroke, Capital Medical University, Beijing, China
3. ³Department of Neurology, University of California, San Francisco, CA, USA
4. ⁴Medical School, University of Western Australia, Perth, WA, Australia
5. ⁵Perron Institute for Neurological and Translational Science, Perth, WA, Australia
6. ⁶Department of Neurology, Liaocheng Third People’s Hospital, Shandong, China
7. ⁷Department of Neurology, Yantai Penglai Traditional Chinese Medicine Hospital, Shandong, China
8. ⁸Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China
9. ⁹Department of Neurology, Liaocheng People’s Hospital, Shandong, China
10. ¹⁰Department of Neurology, The People’s Hospital of Qihe County, Shandong, China
11. ¹¹Department of Neurology, Qinghe People’s Hospital, Hebei, China
12. ¹²Department of Neurology, The Fourth People’s Hospital of Hengshui, Hebei, China
13. ¹³Department of Neurology, Zibo Municipal Hospital, Shandong, China
14. ¹⁴Department of Neurology, Hejian People’s Hospital, Hebei, China
15. ¹⁵Department of Neurology, Suixian Chinese Medicine Hospital, Henan, China
16. ¹⁶Department of Neurology, Jiyuan Hospital of TCM, Henan, China
17. ¹⁷Department of Neurology, Weihai Wendeng District People's Hospital, Shandong, China

1. Correspondence to: Y Wang yongjunwang{at}ncrcnd.org.cn

• Accepted 5 May 2024

Abstract

Objectives To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).

Design Multicentre, double blind, randomised, placebo controlled trial.

Setting 244 hospitals in China between 11 August 2022 and 13 April 2023.

Participants 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled.

Interventions Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days.

Main outcome measures The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat.

Results 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83).

Conclusions The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L.

Trial registration ClinicalTrials.gov, NCT05439356.

Footnotes

• Contributors: A full list of the CHANCE-3 investigators is provided in the appendix. JL, XM, F-DS, and JJ contributed equally to the manuscript. JL, XM, F-DS, JJ, and YW prepared the first draft of the report. HL, F-DS, SCJ, GJH, DE, YW, XZ, ZL, LL, and HZ conceptualised the study design and provided critical comments for the manuscript. YJ and WY managed the data. HG, AW, and YP calculated the sample size and developed the statistical plan. H-QG and AJ did the statistical analyses, with supervision by HL. All other authors were local investigators or co-investigators and recruited participants, collected data, revised the final version of the manuscript, and critically reviewed the report and approved the final version before submission. The steering committee was responsible for the overall design, protocol development, interpretation, and supervision of the trial. The trial executive committee implemented the study. The corresponding author acted as the guarantor for the study, had full access to all the data in the study, had final responsibility for the decision to submit for publication, and attested that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

• Funding: National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. The trial drugs and matching placebo were provided free of charge by Kunming Pharmaceuticals, which had no role in the trial design or conduct, data analysis, or manuscript preparation. The Data Management and Statistics Center at the China National Clinical Research Center for Neurological Diseases was responsible for the data management and statistical analyses. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report or the decision to submit the manuscript.

• Declaration of interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from National Key R&D Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

• Transparency: The corresponding author affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.

• Dissemination to participants and related patient and public communities: The public media and clinical sites will report the findings of CHANCE-3 and provide the text link to the audiences and patients.

• Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement

Data collected for the study, including de-identified individual participant data and a data dictionary defining each field in the set, can be made available to other researchers on reasonable request and after signing appropriate data sharing agreements. Please send data access requests to the corresponding author. Such requests must be approved by the respective ethics boards and appropriate data custodians.

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