Chronic Remote Ischemic Conditioning in Small Infarctions Associated with Stent-assisted Coiling of Unruptured Intracranial Aneurysms

Официальное название

Chronic Remote Ischemic Conditioning in Small Infarctions Associated with Stent-assisted Coiling of Unruptured Intracranial Aneurysms: a Single-center Randomized Controlled Trial.

Обзор

1. Disease Description Stent-assisted coiling has become an effective treatment modality for intracranial aneurysms. With continuous advancements in periprocedural antiplatelet regimens, the incidence of symptomatic thromboembolic events has significantly decreased. However, the rate of procedure-related microembolic infarctions, which are characterized by punctate hyperintense signals on DWI, remains high (10%-76.5%). The underlying causes of these microembolic infarctions remain controversial and may be associated with factors such as different stent types, sheath types, antiplatelet regimens, intraoperative adverse events (e.g., vascular dissection or spasm), patient age, and procedure duration. While most patients with microembolic infarctions exhibit no overt clinical symptoms, the presence of these infarctions reflects underlying tissue damage, posing potential risks that cannot be ignored. Furthermore, their occurrence highlights insufficient preoperative preparation or intraoperative technical issues, which may increase the likelihood of symptomatic embolism. Therefore, investigating the causes of microembolic infarctions and exploring preventive strategies is of great clinical significance. 2. Intervention Description Remote ischemic conditioning (RIC) involves inducing temporary ischemia in distal vessels to protect target vessels from ischemic and reperfusion injuries. RIC can be performed before, during, or after ischemic events and is widely used in the context of coronary artery ischemia. Some studies have shown that RIC can mitigate ischemia-related injuries in the myocardium, kidneys, and lower limbs following cardiovascular surgeries. Previous research has also demonstrated the neuroprotective effects of RIC in ischemia-reperfusion injuries of the nervous system. For instance, RIC significantly improves outcomes in cerebral small vessel disease (CSVD)-related acute stroke events and ameliorates cognitive impairments associated with CSVD. Moreover, the safety and efficacy of RIC have been validated in other conditions or procedures, such as aneurysmal subarachnoid hemorrhage (aSAH), intracranial atherosclerotic stenosis, and carotid artery stenting. 3. Research Hypothesis Current clinical studies on RIC have primarily focused on acute ischemic stroke (including large artery atherosclerosis and CSVD), spontaneous intracerebral hemorrhage, and subarachnoid hemorrhage. The Remote Ischemic Conditioning for Acute Stroke Trial (RESIST) indicated that RIC effectively improves outcomes in acute strokes related to CSVD, including reducing white matter hyperintensities, infarct volume, and modified Rankin Scale (mRS) scores. A clinical study conducted at the Mayo Clinic demonstrated the safety of remote ischemic preconditioning (RIPC) during intracranial aneurysm coiling. Our center's previous study on "Tirofiban and Procedure-Related Microemboli in Stent-Assisted Aneurysm Coiling" revealed that the incidence of procedure-related microembolic infarctions was 61.1% in the non-tirofiban group and 19.4% in the tirofiban-treated group. However, there is currently a lack of research on the use of RIC for procedure-related microembolic infarctions in stent-assisted aneurysm coiling. This study aims to explore the efficacy of ischemic conditioning treatment, performed preoperatively and postoperatively, in reducing procedure-related microembolic infarctions during standard stent-assisted aneurysm coiling. The primary outcomes include the incidence of acute microembolic infarctions postoperatively and the incidence of symptomatic microembolic infarctions at one month following RIC.

Вмешательства

• Процедура remote ischemic conditioning
  Remote ischemic conditioning (RIC) is applied to the contralateral upper limb, consisting of 5 cycles per session, 2 sessions per day. Each cycle includes 5 minutes of ischemia followed by 5 minutes of reperfusion. The pressure used to occlude the brachial artery is set at 200 mmHg or exceeds baseline systolic pressure by 35 mmHg (intervention group).At least 4 sessions of actual RIC treatment before the procedure.Continued RIC treatment for a minimum of 4 weeks postoperatively.
• Процедура Sham treatment
  Remote ischemic conditioning (RIC) is applied to the contralateral upper limb, consisting of 5 cycles per session, 2 sessions per day. Each cycle includes 5 minutes of ischemia followed by 5 minutes of reperfusion. The pressure used to occlude the brachial artery is set at 20 mmHg.At least 4 sessions of sham RIC treatment before the procedure.Continued sham RIC treatment for a minimum of 4 weeks postoperatively.

Первичные конечные точки

• Efficacy of Remote Ischemic Conditioning (RIC) in Preventing Small Infarctions Associated with Stent-Assisted Aneurysm Coiling [Срок оценки: Within 24 hours after the procedure,]

Вторичные конечные точки (1)

• Efficacy of Chronic Remote Ischemic Conditioning (RIC) in Treating Small Infarctions Associated with Stent-Assisted Aneurysm Coiling [Срок оценки: One month after the procedure]

Критерии участия

Критерии включения

• 1\) Age 18-80; 2) Unruptured aneurysm with surgical indications; 3) Stent assisted aneurysm embolization; 4) Patients were willing to receive ischemic adaptation therapy.

Критерии исключения

• 1\) Age < 18 years old; 2) Complicated with cerebrovascular malformations, moyamoya disease and other hemorrhagic cerebrovascular diseases or history; 3) pregnancy; 4) History of acute myocardial infarction within 1 month; 5) Peripheral vascular disease or peripheral neuropathy of the upper limb; 6) Upper limb vascular and soft tissue injury, or combined with limb deformity; 7) Severe subclavian artery stenosis or occlusion; 8) Poor blood pressure control, upper extremity basal systolic pressure ≥200mmHg; 9) Chronic kidney disease.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Mohammad Seyedsaadat S, Rangel Castilla L, Lanzino G, Cloft HJ, Blezek DJ, Theiler A, Kadirvel R, Brinjikji W, Kallmes DF. Remote ischemic preconditioning for elective endovascular intracranial aneurysm repair: a feasibility study. Neuroradiol J. 2019 Jun;32(3):166-172. doi: 10.1177/1971400919842059. Epub 2019 Apr 3. PMID 30942660
• Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F, Wu W, Shi J, Duan Y, Zhang R, Zhang J, Sun Y, Zhang H, Ling F, Wang Y, Feng W, Ding Y, Ovbiagele B, Ji X. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation. 2017 Apr 4;135(14):1325-1335. doi: 10.1161/CIRCULATIO PMID 28174194
• Meng R, Ding Y, Asmaro K, Brogan D, Meng L, Sui M, Shi J, Duan Y, Sun Z, Yu Y, Jia J, Ji X. Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics. 2015 Jul;12(3):667-77. doi: 10.1007/s13311-015-0358-6. PMID 25956401
• Laiwalla AN, Ooi YC, Liou R, Gonzalez NR. Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage. Transl Stroke Res. 2016 Feb;7(1):42-8. doi: 10.1007/s12975-015-0437-3. Epub 2015 Dec 2. PMID 26630942
• Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, Zheng L, Feng W, Liebeskind DS, Fisher M, Ji X. Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease. Stroke. 2017 Nov;48(11):3064-3072. doi: 10.1161/STROKEAHA.117.017691. Epub 2017 Oct 17. PMID 29042490
• Blauenfeldt RA, Mortensen JK, Hjort N, Valentin JB, Homburg AM, Modrau B, Sandal BF, Gude MF, Berhndtz AB, Johnsen SP, Hess DC, Simonsen CZ, Andersen G. Effect of Remote Ischemic Conditioning in Ischemic Stroke Subtypes: A Post Hoc Subgroup Analysis From the RESIST Trial. Stroke. 2024 Apr;55(4):874-879. doi: 10.1161/STROKEAHA.123.046144. Epub 2024 Feb 1. PMID 38299363
• Eitel I, Stiermaier T, Rommel KP, Fuernau G, Sandri M, Mangner N, Linke A, Erbs S, Lurz P, Boudriot E, Mende M, Desch S, Schuler G, Thiele H. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur Heart J. 2015 Nov 21;36(44):3049-57. doi: 10.1093/eurheartj/ehv463. Epub 201 PMID 26385956
• Luo SJ, Zhou YJ, Shi DM, Ge HL, Wang JL, Liu RF. Remote ischemic preconditioning reduces myocardial injury in patients undergoing coronary stent implantation. Can J Cardiol. 2013 Sep;29(9):1084-9. doi: 10.1016/j.cjca.2012.11.022. Epub 2013 Feb 12. PMID 23414904

Идентификаторы

NCT: NCT06826144 · CRISIS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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