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

NCT06826144 | Not Yet Recruiting

• 1 other identifier: CRISIS
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief Summary

1. 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. 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. 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.

Conditions

Unruptured Intracranial Aneurysm; Infarction Cerebral

Keywords

remote ischemic conditioning

Outcome Measures

Primary Outcomes (1)

• Efficacy of Remote Ischemic Conditioning (RIC) in Preventing Small Infarctions Associated with Stent-Assisted Aneurysm Coiling

  Within 24 hours after the procedure, a brain MRI is performed to record the number and size of hyperintense signals on DWI. The trial group and control group are compared, and the efficacy is assessed based on statistical analysis results. If the mean number of hyperintense signals on DWI in the trial group is lower than that in the control group, with a statistically significant difference, the intervention is considered effective; otherwise, it is considered ineffective.

  Within 24 hours after the procedure,

Secondary Outcomes (1)

• Efficacy of Chronic Remote Ischemic Conditioning (RIC) in Treating Small Infarctions Associated with Stent-Assisted Aneurysm Coiling

  One month after the procedure

Other Outcomes (2)

• The incidence of thrombus formation or embolic events in the limb subjected to RIC in the intervention group.

  24 hours, 2 weeks, and 1 month postoperatively

• The incidence of skin damage or bruising in the RIC group.

  before surgery and 24 hours, 2 weeks, and 1 month postoperatively

Study Arms (2)

RIC

EXPERIMENTAL

All enrolled patients receive standard stent-assisted aneurysm coiling therapy（Patients are required to receive antiplatelet therapy for at least 3 days before the procedure, consisting of:Aspirin: 100 mg once daily, combined with Clopidogrel: 75 mg once daily, or Ticagrelor: 90 mg twice daily）.Depending on intraoperative and postoperative conditions, tirofiban is administered as follows: an initial bolus of 0.6 μg/kg over 3 minutes, followed by continuous intravenous infusion at 0.1 μg/kg/min for 18 hours. 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 At least 4 sessions of actual RIC treatment before the procedure.Continued RIC treatment for a minimum of 4 weeks postoperatively.

Procedure: remote ischemic conditioning

sham

SHAM COMPARATOR

All enrolled patients receive standard stent-assisted aneurysm coiling therapy.（Patients are required to receive antiplatelet therapy for at least 3 days before the procedure, consisting of:Aspirin: 100 mg once daily, combined with Clopidogrel: 75 mg once daily, or Ticagrelor: 90 mg twice daily）.Depending on intraoperative and postoperative conditions, tirofiban is administered as follows: an initial bolus of 0.6 μg/kg over 3 minutes, followed by continuous intravenous infusion at 0.1 μg/kg/min for 18 hours. 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.

Procedure: Sham treatment

Interventions

remote ischemic conditioning PROCEDURE

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.

Also known as: RIC

RIC

Sham treatment PROCEDURE

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.

sham

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Related Publications (13)

• 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 BACKGROUND

• 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/CIRCULATIONAHA.116.024807. Epub 2017 Feb 7.

  PMID: 28174194 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 2015 Sep 17.

  PMID: 26385956 BACKGROUND

• 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 BACKGROUND

• Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.

  PMID: 18456674 BACKGROUND

• Bell R, Yellon D. Surgery: Remote ischaemic conditioning--approaching prime time? Nat Rev Cardiol. 2013 Nov;10(11):619-21. doi: 10.1038/nrcardio.2013.154. Epub 2013 Sep 24. No abstract available.

  PMID: 24060957 BACKGROUND

• Kim DY, Park JC, Kim JK, Sung YS, Park ES, Kwak JH, Choi CG, Lee DH. Microembolism after Endovascular Treatment of Unruptured Cerebral Aneurysms: Reduction of its Incidence by Microcatheter Lumen Aspiration. Neurointervention. 2015 Sep;10(2):67-73. doi: 10.5469/neuroint.2015.10.2.67. Epub 2015 Sep 2.

  PMID: 26389009 BACKGROUND

• Park JC, Lee DH, Kim JK, Ahn JS, Kwun BD, Kim DY, Choi CG. Microembolism after endovascular coiling of unruptured cerebral aneurysms: incidence and risk factors. J Neurosurg. 2016 Mar;124(3):777-83. doi: 10.3171/2015.3.JNS142835. Epub 2015 Sep 18.

  PMID: 26381257 BACKGROUND

• Bendszus M, Koltzenburg M, Burger R, Warmuth-Metz M, Hofmann E, Solymosi L. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: a prospective study. Lancet. 1999 Nov 6;354(9190):1594-7. doi: 10.1016/S0140-6736(99)07083-X.

  PMID: 10560674 BACKGROUND

MeSH Terms

Conditions

Cerebral Infarction

Condition Hierarchy (Ancestors)

Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Yifei Wang

CONTACT

+86-13852665323; wangyifei5323@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Standard Treatment All enrolled patients receive standard stent-assisted aneurysm coiling therapy. Depending on intraoperative and postoperative conditions, tirofiban is administered as follows: an initial bolus of 0.6 μg/kg over 3 minutes, followed by continuous intravenous infusion at 0.1 μg/kg/min for 18 hours. RIC Treatment Protocol 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) or 20 mmHg (control group). Group Assignments Group A (Control Group): At least 4 sessions of sham RIC treatment before the procedure. Continued sham RIC treatment for a minimum of 4 weeks postoperatively. Group B (Intervention Group): At least 4 sessions of actual RIC treatment before the procedure. Cont

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 13, 2025
• Study Start: February 20, 2025
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 13, 2025

Record last verified: 2025-01