Clinical trial NCT05032053: Antithrombotic Drug Use in Patients With Ischemic Stroke and Microbleeds
Official title: Antithrombotic Drug Use in Patients With Ischemic Stroke and Microbleeds
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
Keywords: Ischemic Stroke
microbleeds
Proteomics
antithrombotic drug
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
Collaborators: name: Ankang Central Hospital
name: Yan'an University Affiliated Hospital
First posted: 2021-09-02
Enrollment: 3000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The population we observed are hospitalized patients with new cerebral infarction and met the inclusion criteria(without exclusion criteria). The method of consecutive participant sampling is used to collect the included population.

Brief summary: To observe the effect of different antithrombotic drugs on the prognosis of ischemic stroke patients with cerebral microbleeds. And further combined with proteomic methods to explore serological markers that can be used to accurately predict the prognosis of such patients.

Detailed description: Cerebral microbleeds (CMBs) are caused by microvascular lesions in the brain, which is a subclinical deposition of hemosiderin after the damage of microvascular. Antithrombotic drug are widely used in the secondary prevention of patients with ischemic stroke. Studies have shown that antithrombotic drug can increase the incidence of intracranial hemorrhage in ischemic stroke patients with cerebral microbleeds. For such patients, how to carry out effective and safe antithrombotic therapy is still unclear.

We will study from two aspects: 1) We designed a cohort registration study to observe the prognosis and progress of CMBs in ischemic stroke patients one year after using various antithrombotic drugs. 2) Data independent acquisition quantitative proteomics (DIA quantitative proteomics) will be used to screen serum protein markers that may affect the prognosis of ischemic stroke patients with CMBs.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed clinically as ischemic stroke;
2. Age ≥ 40 years;
3. Onset time ≤ 3 months;
4. Informed consent was signed.

Exclusion Criteria:

1. Patients with symptomatic intracranial hemorrhage;
2. bleeding lesion \> 10 mm was found on SWI;
3. Vascular malformations, tumors, abscesses or other major non ischemic brain diseases were present;
4. There are contraindications for antithrombotic drugs use;
5. Serious systemic diseases;
6. Refusal to sign informed consent or poor compliance.

Primary outcomes:
measure: Increase of cerebral microbleeds
timeFrame: 1 year after onset
Secondary outcomes:
measure: Stroke recurrence rate
timeFrame: 1 year after onset
measure: The incidence of cerebral hemorrhage
timeFrame: 1 year after onset
Other outcomes:
Locations:
city: Ankang
country: China
facility: Ankang Central Hospital
state: Shaanxi
city: Hanzhong
country: China
facility: 3201 Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Department of Neurology, Xijing Hospital, Fourth Military Medical University
state: Shaanxi
city: Ya'an
country: China
facility: Yan'an University Affiliated Hospital
state: Shaanxi
city: Yunlin
country: China
facility: Yulin No.2 Hospital
state: Shaanxi
city: Xi'AN
country: China
facility: Xi'AN GAOXIN Hospital
state: Shannxi
city: Hanzhong
country: China
facility: Hanzhong People's Hospital
city: Xi'An
country: China
facility: 986 Hospital
city: Xi'an
country: China
facility: Gaoling District Hospital
city: Xi'an
country: China
facility: Gem Flower Xi'an Changqing Staff Hospital
city: Xi'an
country: China
facility: Tangdu Hospital
city: Xi'AN
country: China
facility: The First Affiliated Hospital of Xi'an Medical University
city: Xianyang
country: China
facility: No.215 Hospital of Shaanxi nuclear industry
city: Xianyang
country: China
facility: The First People's Hospital of Xianyang
city: Xianyang
country: China
facility: Xian Yang Central Hospital
city: Yan'an
country: China
facility: Yan'an People's Hospital
Study officials:
affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University
name: Wen Jiang, Ph.D
role: STUDY_DIRECTOR
References:
citation: Wilson D, Ambler G, Shakeshaft C, Brown MM, Charidimou A, Al-Shahi Salman R, Lip GYH, Cohen H, Banerjee G, Houlden H, White MJ, Yousry TA, Harkness K, Flossmann E, Smyth N, Shaw LJ, Warburton E, Muir KW, Jager HR, Werring DJ; CROMIS-2 collaborators. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol. 2018 Jun;17(6):539-547. doi: 10.1016/S1474-4422(18)30145-5. Epub 2018 May 16.
citation: Shoamanesh A, Hart RG, Connolly SJ, Kasner SE, Smith EE, Marti-Fabregas J, Liu YY, Uchiyama S, Mikulik R, Veltkamp R, O'Donnell MJ, Ntaios G, Muir KW, Field TS, Santo GC, Olavarria V, Mundl H, Lutsep H, Berkowitz SD, Sharma M. Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA Neurol. 2021 Jan 1;78(1):11-20. doi: 10.1001/jamaneurol.2020.3836.
citation: Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007 Aug;130(Pt 8):1988-2003. doi: 10.1093/brain/awl387. Epub 2007 Feb 24.
citation: Nandigam RN, Viswanathan A, Delgado P, Skehan ME, Smith EE, Rosand J, Greenberg SM, Dickerson BC. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol. 2009 Feb;30(2):338-43. doi: 10.3174/ajnr.A1355. Epub 2008 Nov 11.
citation: Vernooij MW, Haag MD, van der Lugt A, Hofman A, Krestin GP, Stricker BH, Breteler MM. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol. 2009 Jun;66(6):714-20. doi: 10.1001/archneurol.2009.42. Epub 2009 Apr 13.
citation: Liu S, Li C. Antiplatelet Drug Use and Cerebral Microbleeds: A Meta-analysis of Published Studies. J Stroke Cerebrovasc Dis. 2015 Oct;24(10):2236-44. doi: 10.1016/j.jstrokecerebrovasdis.2015.05.022. Epub 2015 Aug 10.
citation: Lau KK, Lovelock CE, Li L, Simoni M, Gutnikov S, Kuker W, Mak HKF, Rothwell PM. Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review. Stroke. 2018 Jun;49(6):1434-1442. doi: 10.1161/STROKEAHA.117.020104. Epub 2018 May 10.
citation: Cheng Y, Wang Y, Song Q, Qiu K, Liu M. Use of anticoagulant therapy and cerebral microbleeds: a systematic review and meta-analysis. J Neurol. 2021 May;268(5):1666-1679. doi: 10.1007/s00415-019-09572-x. Epub 2019 Oct 15.
citation: Charidimou A, Boulouis G, Shams S, Calvet D, Shoamanesh A; International META-MICROBLEEDS Initiative. Intracerebral haemorrhage risk in microbleed-positive ischaemic stroke patients with atrial fibrillation: Preliminary meta-analysis of cohorts and anticoagulation decision schema. J Neurol Sci. 2017 Jul 15;378:102-109. doi: 10.1016/j.jns.2017.04.042. Epub 2017 Apr 28.
citation: MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation. Neurology. 2019 Sep 3;93(10):465. doi: 10.1212/WNL.0000000000007920. No abstract available.
citation: Kimura K, Aoki J, Shibazaki K, Saji N, Uemura J, Sakamoto Y. New appearance of extraischemic microbleeds on T2*-weighted magnetic resonance imaging 24 hours after tissue-type plasminogen activator administration. Stroke. 2013 Oct;44(10):2776-81. doi: 10.1161/STROKEAHA.113.001778. Epub 2013 Jul 25.
citation: Shoamanesh A, Yan S, Charidimou A. New Cerebral Microbleeds and Mechanism of Post-Thrombolysis Remote Intracerebral Hemorrhage: "Red Meets White" Revisited. Front Neurol. 2015 Sep 15;6:203. doi: 10.3389/fneur.2015.00203. eCollection 2015. No abstract available.
citation: Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J. Higher ambulatory blood pressure relates to new cerebral microbleeds: 2-year follow-up study in lacunar stroke patients. Stroke. 2013 Apr;44(4):978-83. doi: 10.1161/STROKEAHA.111.676619. Epub 2013 Feb 28.
citation: Gregoire SM, Brown MM, Kallis C, Jager HR, Yousry TA, Werring DJ. MRI detection of new microbleeds in patients with ischemic stroke: five-year cohort follow-up study. Stroke. 2010 Jan;41(1):184-6. doi: 10.1161/STROKEAHA.109.568469. Epub 2009 Nov 5.