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Randomized Controlled Trial
. 2024 Jun 26:385:e079061.
doi: 10.1136/bmj-2023-079061.

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

Jiejie Li  1 , Xia Meng  1 , Fu-Dong Shi  1 , Jing Jing  1 , Hong-Qiu Gu  1 , Aoming Jin  1 , Yong Jiang  1 , Hao Li  1 , S Claiborne Johnston  2 , Graeme J Hankey  3   4 , J Donald Easton  2 , Liguo Chang  5 , Penglai Shi  6 , Lihua Wang  7 , Xianbo Zhuang  8 , Haitao Li  9 , Yingzhuo Zang  10 , Jianling Zhang  11 , Zengqiang Sun  12 , Dongqi Liu  13 , Ying Li  14 , Hongqin Yang  15 , Jinguo Zhao  16 , Weiran Yu  1 , Anxin Wang  17 , Yuesong Pan  1 , Jinxi Lin  1 , Xuewei Xie  1 , Wei-Na Jin  1 , Shuya Li  1 , Siying Niu  1 , Yilong Wang  17 , Xingquan Zhao  1 , Zixiao Li  1 , Liping Liu  1 , Huaguang Zheng  1 , Yongjun Wang  17   18 ; CHANCE-3 Investigators
Affiliations
Randomized Controlled Trial

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

Jiejie Li et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

Fig 1
Fig 1
Enrolment and randomisation of the patients. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe stroke. The ABCD2 score assesses the risk of stroke on the basis of age, blood pressure, clinical features, duration of transient ischaemic attack, and the presence or absence of diabetes mellitus, with scores ranging from 0 to 7 and higher scores indicating greater risk. hs-CRP=high sensitivity C-reactive protein; TIA=transient ischaemic stroke
Fig 2
Fig 2
Cumulative incidence of any new stroke (primary outcome) within 90 days. The bottom graph shows the same data on an enlarged Y axis. The event risk and hazard ratio were estimated by Kaplan-Meier method and Cox models without consideration of competing risk of death. P value was calculated from Cox model
Fig 3
Fig 3
Hazard ratio for any new stroke in prespecified subgroups within 90 days. The body mass index is the weight in kilograms divided by the square of the height in metres
See this image and copyright information in PMC

References

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