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

NCT ID: NCT06826144

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2026-06-01

Brief Summary

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.

Conditions

Unruptured Intracranial Aneurysm; Infarction Cerebral

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

RIC

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.

Group Type: EXPERIMENTAL

remote ischemic conditioning

Intervention Type: 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.

sham

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.

Group Type: SHAM_COMPARATOR

Sham treatment

Intervention Type: 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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: PROCEDURE

Other Intervention Names

RIC

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Lu Hua

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Yifei Wang

Role: CONTACT

wangyifei5323@163.com

+86-13852665323

References

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.

Reference Type: BACKGROUND

PMID: 30942660 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28174194 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25956401 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26630942 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29042490 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38299363 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26385956 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23414904 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18456674 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24060957 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26389009 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26381257 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10560674 (View on PubMed)

Other Identifiers

CRISIS

Identifier Type: -

Identifier Source: org_study_id