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

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Research BMJ 2024; 385 doi: https://doi.org/10.1136/bmj-2023-079061 (Published 26 June 2024) Cite this as: BMJ 2024;385:e079061

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  • Peer review
  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 WangColchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial (1), 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.

http://creativecommons.org/licenses/by/4.0/

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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

FAQs

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

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.

What are the odds of having a stroke after a TIA? ›

Estimates of 90-day stroke risk after TIA range from 10% to 18% and highlight the importance of rapid evaluation and initiation of secondary prevention strategies in the emergency department (ED).

What is the secondary prevention medication for a transient ischemic attack? ›

The most commonly recommended antiplatelet agents for secondary stroke prevention in North America and Europe are acetylsalicylic acid (ASA, 75 to 325 mg/day), clopidogrel, and the combination of ASA and extended-release dipyridamole.

What medication is prescribed after a TIA? ›

Aspirin is the most commonly used anti-platelet medicine. Aspirin is also the least expensive treatment with the fewest potential side effects. An alternative to aspirin is the anti-platelet drug clopidogrel (Plavix). Aspirin and clopidogrel may be prescribed together for about a month after the TIA .

Is colchicine used to prevent strokes? ›

Conclusion: Colchicine was associated with an overall reduction in the risk of incidence of stroke, MI, MACE, ACS in patients with coronary heart disease. However, no such effect was observed with mortality.

Does a TIA mean a bigger stroke is coming? ›

It's a warning sign, not a “mini-stroke.”

“In some ways, people who have a TIA are actually very fortunate. It's a warning that they are at high risk of a stroke that could cause permanent deficits,” Streib said.

How to avoid a stroke after TIA? ›

If you've already had a TIA, making these changes can help reduce your risk of having a full stroke or another TIA in the future.
  1. Diet. ...
  2. Exercise. ...
  3. Stop smoking. ...
  4. Cut down on alcohol. ...
  5. Managing underlying conditions.

Can you recover from transient ischemic attack? ›

A person may have one or many TIAs. People recover completely from the symptoms of a TIA. A TIA is a warning sign that a person may be at high risk for a stroke, which could cause severe impairment. Immediate treatment can decrease or eliminate this risk.

What are the warning signs of a TIA? ›

Symptoms may include:
  • Sudden numbness or weakness of the face, arm or leg, especially on one side of the body.
  • Sudden confusion.
  • Sudden trouble speaking.
  • Sudden trouble seeing in one or both eyes.
  • Sudden trouble walking.
  • Sudden dizziness, loss of balance or coordination.
  • Sudden, severe headache with no known cause.

Can you have a mini stroke while on blood thinners? ›

Unfortunately, the blood thinners used to prevent such blood clots can increase the risk of bleeding in the brain, a cause of hemorrhagic stroke.

What is the best drink to avoid stroke? ›

To recap, your best choices are hydrating beverages that contain minimal calories, sugar or salt. Reach for water, coffee or tea most often. And keep a water bottle handy – the visual cue reminds you to keep sipping.

What heals the brain after a stroke? ›

Brain exercises can help people regain thinking, reasoning, and memory skills after a stroke. Other brain-strengthening activities include eating a heart-healthy diet, getting regular exercise, and limiting alcohol consumption. Stroke recovery begins before you leave the hospital.

When is the most critical time after TIA? ›

TIAs do not cause lasting damage to the brain. But, TIAs are a warning sign that you may have a true stroke in the coming days or months. Some people who have a TIA will have a stroke within 3 months. Half of these strokes happen during the 48 hours after a TIA.

Who should avoid colchicine? ›

Who may not be able to take colchicine
  • have ever had an allergic reaction to colchicine or any other medicine.
  • have a severe blood disorder, such as low amounts of white or red blood cells, a low blood platelet count or problems with your bone marrow function.
  • have severe kidney or liver problems.

Is colchicine high risk? ›

However, when taken in excess, colchicine can cause serious and often fatal poisoning.

Why would a cardiologist prescribe colchicine? ›

It works broadly to reduce inflammation by disrupting tubulin polymerization. Colchicine decreases interleukin-1 beta production through inactivation of the NLRP3 inflammasome pathway, which has been associated with the inflammatory component driving atherosclerotic plaque progression and instability.

How long after a TIA will you have a stroke? ›

TIAs do not cause lasting damage to the brain. But, TIAs are a warning sign that you may have a true stroke in the coming days or months. Some people who have a TIA will have a stroke within 3 months. Half of these strokes happen during the 48 hours after a TIA.

What is the life expectancy after a TIA stroke? ›

A 2019 research review states that people who experienced a TIA had a 4% lower relative survival rate in the first year after the attack. Over the next 9 years, the relative survival rate was 20% lower. Experiencing a TIA increases the risk of stroke, particularly within the first couple of months following the event.

How likely is it to have a second TIA? ›

Most people, and even many doctors, don't realize that the risk of a second stroke is as high as 12.8 percent in the first week after a TIA (transient ischemic attack). If you do not change certain lifestyle factors, the risk of a second stroke within the next five years can be as high as 30 percent.

What is the average age for a TIA? ›

age – although TIAs can happen at any age (including in children and young adults), they're most common in people over 55.

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