China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis

NCT01763320 | Completed Phase 3 DMC

• 1 other identifier: XW125-S002
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment, however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience, neither regarding natural history, nor treatment complications rate. As ICAS is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective randomized multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. The China Angioplasty \& Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial, is an ongoing, government-funded, prospective, multicenter randomized trial. It recruits patients with recent TIA or stroke caused by 70-99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume center with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days The CASSISS trial will be conducted in 8 sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 subjects (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by Dec, 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high volume centers.

Conditions

Ischemic Stroke

Keywords

ischemic stroke; intracranial stenting; vascular risk factor management

Outcome Measures

Primary Outcomes (1)

• stroke or death within 30 days after enrollment, any stroke in the territory of the symptomatic intracranial artery beyond 30 days through 12 months

  the number of participants who suffer from stroke or death within 30 days after enrollment, or any stroke in the territory of the symptomatic intracranial artery beyond 30 days through 12 months

  12 months

Secondary Outcomes (5)

• the number of participants who suffer from disabling stroke or death

  within 3 years

• the number of participants who suffer from stroke in the territory of qualifying artery

  within 2 years

• the number of participants who suffer from stroke in the territory of qualifying artery

  within 3 years

• the number of participants who survives in both groups

  within 3 years

• the number of participants who suffer from any stroke,TIA, or cardiovascular events

  within 3 years

Other Outcomes (7)

• the number of participants who suffer from stroke or death within 30 days after enrollment

  within 30 days after enrollment

• the number of participants who suffer from any stroke, death in the territory of the symptomatic intracranial artery beyond 30 days through 12 months

  beyond 30 days through 12 months

• the rate of restenosis (>50%) related to stenting within a follow-up of 36 months

  within a follow-up of 36 months

Study Arms (2)

Intracranial stenting group

EXPERIMENTAL

all the participants in this group will be performed with intracranial stenting

Procedure: Intracranial stenting group

medical group

ACTIVE COMPARATOR

all the participants in this group will be given medical therapy including aspirin 100mg + clopidogrel 75mg per day for 90 consecutive days and clopidogrel 75mg per day thereafter

Drug: medical group

Interventions

Intracranial stenting group PROCEDURE

all the participants in this group will be performed with intracranial stenting

Intracranial stenting group

medical group DRUG

all the participants in this group will be given medical therapy including aspirin 100mg + clopidogrel 75mg per day for 90 consecutive days and clopidogrel 75mg per day thereafter

medical group

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients aged between 30-80 years; intracranial arterial stenosis related to the following non-atherosclerotic factors will be not be considered: arterial dissection, moya-moya disease; vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid pleocytosis; radiation-induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process, and suspected recanalized embolus;
• Symptomatic ICAS: presented with TIA or stroke within the past 12 months attributed to 70%-99% stenosis of a major intracranial artery (internal carotid artery, MCA \[M1\], vertebral artery, or basilar artery);
• Degree of stenosis: 70%-99%; stenosis degree must be confirmed by catheter angiography for enrollment in the trial;
• There might be remote infarctions on MRI scan, which could be accounted by the occlusion of the terminal cortical branches or hemodynamic compromise (perforator occlusion excluded). Infarction due to perforators occlusion is defined as basal ganglia or brainstem/thalamus infarction related with MCA or BA stenosis;
• Expected ability to deliver the stent to the lesion;
• All the patients should be performed with stenting beyond a duration of 3 weeks from the latest ischemic symptom onset;
• No recent infarctions identified on MRI (indicated as high signals on DWI series) upon enrollment;
• No massive cerebral infarction (\>1/2 MCA territory), intracranial hemorrhage, epidural or sub-dural hemorrhage, and intracranial brain tumor on CT or MRI scan;
• mRS scale score of \<=2;
• Target vessel reference diameter must be measured to be 2.00 mm to 4.50 mm; target area of stenosis is \<=14 mm in length;
• No childbearing potential or has a negative pregnancy test within the past 1 week prior to study procedure; female patients had normal menses in the last 18 months;
• Patient is willing and able to return for all follow-up visits required by the protocol;
• Patients understand the purpose and requirements of the study and have signed informed consent form.

You may not qualify if:

• Refractory to general anesthesia; patients were not able to be overcome by pre-treatment with medical therapy.
• Any condition that precludes proper angiographic assessment.
• Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion.
• Bilateral intracranial VA stenosis of 70%-99% and uncertainty about which lesion is symptomatic (e.g., if patient has pon, midbrain, temporal and occipital symptoms).
• Presence of a previously placed intravascular stent or graft in the ipsilateral distribution within 30 days.
• Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion.
• Severe vascular tortuosity or anatomy that would preclude the safe introduction of a guiding catheter, guiding sheath or stent placement.
• Plan to perform concomitant angioplasty or stenting of an extracranial. vessel tandem to an ipsilateral intracranial stenosis.
• Presence of intraluminal thrombus proximal to or at the target lesion.
• Any aneurysm proximal to or distal to intracranial stenotic artery.
• Intracranial tumors or any intracranial vascular malformations.
• Computed tomographic or angiographic evidence of severe calcification at target lesion.
• Thrombolytic therapy within 24 hours before enrollment.
• Evolving stroke or progressive neurologic signs within 24 hours before enrollment.
• Stroke of sufficient size (\>5cm on CT or MRI) to place patient at risk of hemorrhagic transformation during the procedure; hemorrhagic transformation of an ischemic stroke within the past 15 days.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Department of neurosurgery, Xuanwu hospital

Beijing, 100053, China

Location

Related Publications (10)

• Feigin VL. Stroke epidemiology in the developing world. Lancet. 2005 Jun 25-Jul 1;365(9478):2160-1. doi: 10.1016/S0140-6736(05)66755-4. No abstract available.

  PMID: 15978910 BACKGROUND

• Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7.

  PMID: 21899409 RESULT

• Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano JG; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16. doi: 10.1056/NEJMoa043033.

  PMID: 15800226 RESULT

• Zaidat OO, Klucznik R, Alexander MJ, Chaloupka J, Lutsep H, Barnwell S, Mawad M, Lane B, Lynn MJ, Chimowitz M; NIH Multi-center Wingspan Intracranial Stent Registry Study Group. The NIH registry on use of the Wingspan stent for symptomatic 70-99% intracranial arterial stenosis. Neurology. 2008 Apr 22;70(17):1518-24. doi: 10.1212/01.wnl.0000306308.08229.a3. Epub 2008 Jan 30.

  PMID: 18235078 RESULT

• Fiorella D, Levy EI, Turk AS, Albuquerque FC, Niemann DB, Aagaard-Kienitz B, Hanel RA, Woo H, Rasmussen PA, Hopkins LN, Masaryk TJ, McDougall CG. US multicenter experience with the wingspan stent system for the treatment of intracranial atheromatous disease: periprocedural results. Stroke. 2007 Mar;38(3):881-7. doi: 10.1161/01.STR.0000257963.65728.e8. Epub 2007 Feb 8.

  PMID: 17290030 RESULT

• Derdeyn CP, Chimowitz MI, Lynn MJ, Fiorella D, Turan TN, Janis LS, Montgomery J, Nizam A, Lane BF, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Lynch JR, Zaidat OO, Rumboldt Z, Cloft HJ; Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2014 Jan 25;383(9914):333-41. doi: 10.1016/S0140-6736(13)62038-3. Epub 2013 Oct 26.

  PMID: 24168957 RESULT

• Gao P, He X, Wang H, Wang T, Wang D, Shi H, Li T, Zhao Z, Cai Y, Wu W, He W, Yu J, Zheng B, Feng X, Derdeyn CP, Dmytriw AA, Wu Y, Zhao G, Jiao L; CASSISS Trial Investigators. Stenting Versus Medical Therapy for Symptomatic Intracranial Artery Stenosis: Long-Term Follow-Up of a Randomized Trial. Stroke. 2025 May;56(5):1128-1137. doi: 10.1161/STROKEAHA.124.049602. Epub 2025 Mar 18.

  PMID: 40099362 DERIVED

• Wang T, Luo J, Li T, Almallouhi E, Gao P, Gong H, Zhang X, Wang J, Lu T, Yang Y, Yang R, Xing Z, Wang H, Derdeyn CP, Jiao L. Stenting versus medical treatment alone for symptomatic intracranial artery stenosis: a preplanned pooled individual patient data analysis. J Neurointerv Surg. 2025 Sep 12;17(10):1032-1039. doi: 10.1136/jnis-2024-022189.

  PMID: 39147573 DERIVED

• Gao P, Wang T, Wang D, Liebeskind DS, Shi H, Li T, Zhao Z, Cai Y, Wu W, He W, Yu J, Zheng B, Wang H, Wu Y, Dmytriw AA, Krings T, Derdeyn CP, Jiao L; CASSISS Trial Investigators. Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial. JAMA. 2022 Aug 9;328(6):534-542. doi: 10.1001/jama.2022.12000.

  PMID: 35943472 DERIVED

• Gao P, Wang D, Zhao Z, Cai Y, Li T, Shi H, Wu W, He W, Yin L, Huang S, Zhu F, Jiao L, Ji X, Qureshi AI, Ling F. Multicenter Prospective Trial of Stent Placement in Patients with Symptomatic High-Grade Intracranial Stenosis. AJNR Am J Neuroradiol. 2016 Jul;37(7):1275-80. doi: 10.3174/ajnr.A4698. Epub 2016 Feb 11.

  PMID: 26869472 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Liqun Jiao, MD

  Xuanwu Hospital, Capital University of Medical Sciences, Beijing, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD.PhD

Study Record Dates

• First Submitted: January 6, 2013
• First Posted: January 8, 2013
• Study Start: March 5, 2014
• Primary Completion: November 10, 2016
• Study Completion: November 10, 2019
• Last Updated: May 12, 2022

Record last verified: 2022-05

Locations

CN (1)