China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Xuanwu Hospital, Beijing
Sponsor:
Information provided by (Responsible Party):
Xuanwu Hospital, Beijing
ClinicalTrials.gov Identifier:
NCT01763320
First received: January 6, 2013
Last updated: June 4, 2013
Last verified: December 2012
  Purpose

SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) hasn't received the expected results; however, it does not mean that clinical exploration on intracranial treatment come to a full stop. On the contrary, a discrepancy on reported data between multi-centre RCT and most single center studies urges us for thorough investigation in future.

CASSISS is an investigator-initiated, government-funded RCT that will determine whether intracranial stenting and best medical therapy is superior to aggressive medical therapy alone for preventing stroke during a mean follow-up of three years in patients with symptomatic stenosis of a major intracranial artery (MCA, carotid, vertebral, basilar). This trial was launched by Xuanwu Hospital, Capital University of Medical Science, with 10 collaborators participating. Enrollment will begin in 2013, and it aims to have a sample size of 520 subjects (PTAS, 260; medication, 260) in 3 years. The trial is scheduled to complete in 2015.

SAMMPRIS is flawed with defect in design, heterogeneity in experience and credentials of operators and high rate of complication; some questions have been raised, and remained resolved. CASSISS has been modified based on SAMMPRIS in order to acquire the data for China:

Technique, experience, and credential of the operators are closely related with perioperative complications in PTAS. The investigators select 10 representatives from 40 large-scale medical centers for participation on the basis of geographical distribution. All the participants are ranked as top in China. They have the most experienced surgeons or interventionist in China, and are fully qualified for this trial. This will guarantee the success and safety of technique, maintain the continuity of operator's experience, and make the complication rate as low as possible.

Pre-CASSISS registry trial:

A registry pilot trial will be performed prior to CASSISS. It aims to test the credentialing of interventionists and participating centers. As for the candidate centers, the following aspects will be considered: PTAS experiences, peri-operative complications, and the number of accumulated PTAS cases in each center. Centers are required to have a team consisting of a neurologist, an interventionist, a neurosurgeon, and a research coordinator. All the centers involved are required to to perform a competitive registration study of recruiting a consecutive 100 PTAS as a pool together as a registration trial within duration of 6 months. Certification was achieved by participating centers, whose clinical results are audited by means of a validated selection process documenting that they have performed more than 5 procedures within this period and that the rates of complications (morbidity and mortality) are less than 15%. Those who will not satisfy the certification criterion will be excluded from the final trial.

The 3rd-party company is employed to provide trial design, management, supervision, and quality control service.

The 30-day rate of stroke or death associated with stenting in the SAMMPRIS trial (14.7%) is nearly 2.5 times as high as CREST, one third of which is symptomatic intracranial hemorrhage. It was thought because of reperfusion hemorrhage since the median time from qualifying event to randomization in SAMMPRIS is one week only. The investigators modify one of inclusion criteria that all the recruited patients routinely undergo MRI plus DWI (diffusion-weighted imaging) scans to exclude any possible new lesions. In case of new infarction identified on DWI (diffusion-weighted imaging) or qualifying event confirmed by neurologist, the patient will be rescheduled for randomization one month later.

SAMMPRIS was stopped ahead of schedule due to the safety concern. More than half of the PTAS patients were lost for follow-up at 1 year, and the remaining were followed up with a mean duration less than 1 year. It leaves the question of long-time follow-up data open. Base on SAMMPRIS, the investigators' trial will conduct a systematic follow-up system. Upon recruitment, all the patients' neurological and imaging examination will be determined at baseline, 1 week, 1 month, 1 year, and 2 year after surgery, respectively.


Condition Intervention Phase
Ischemic Stroke
Procedure: Intracranial stenting group
Drug: medical group
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A Prospective Multi-center, Randomized Controlled Trial (RCT)

Resource links provided by NLM:


Further study details as provided by Xuanwu Hospital, Beijing:

Primary Outcome Measures:
  • the number of participants who suffer from Ischemic stroke, death or cardiovascular events after enrollment or after any revascularization procedure of the qualifying lesion in the territory of the symptomatic intracranial artery [ Time Frame: up to 30 days ] [ Designated as safety issue: Yes ]
    the number of participants who suffer from Ischemic stroke, death or cardiovascular events after enrollment or any revascularization procedure of the qualifying lesion in the territory of the symptomatic intracranial artery

  • the number of participants who suffer from Ischemic stroke, death or cardiovascular events after enrollment or after any revascularization procedure of the qualifying lesion in the territory of the symptomatic intracranial artery [ Time Frame: beyond 30 days to 12 months ] [ Designated as safety issue: No ]
    the number of participants who suffer from Ischemic stroke, death or cardiovascular events after enrollment or after any revascularization procedure of the qualifying lesion in the territory of the symptomatic intracranial artery


Secondary Outcome Measures:
  • the number of participants who suffer from disabling stroke or death [ Time Frame: beyond 30 days through 36 months ] [ Designated as safety issue: No ]
    the number of participants who suffer from disabling stroke or death

  • the number of participants who suffer from restenosis (>50%) related to intracranial stenting [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    the number of participants who suffer from restenosis (>50%) related to intracranial stenting

  • the number of participants who suffer from any stroke, severe transient ischemic attack (TIA), cardiovascular events related to intracranial stenting or medical therapy [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    the number of participants who suffer from any stroke, severe transient ischemic attack (TIA), cardiovascular events related to intracranial stenting or medical therapy

  • the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index [ Time Frame: at 7 days, 30 days, 6 months, 12 months, 24 months and 36 months ] [ Designated as safety issue: No ]
    the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index

  • the number of participants who survives in both groups [ Time Frame: beyond 12 months to 36 months ] [ Designated as safety issue: No ]
    the number of participants who survives in both groups


Estimated Enrollment: 380
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intracranial stenting group
all the participants in this group will be performed with intracranial stenting
Procedure: Intracranial stenting group
all the participants in this group will be performed with intracranial stenting
Other Name: Intracranial stenting group
Active Comparator: medical group
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
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
Other Name: medical group

Detailed Description:

Over two-thirds of stroke deaths worldwide are in developing countries, and China has the largest population among developing countries. Unlike in western countries, cerebrovascular disease predominates; the number of patients who die from stroke is more than three times that from coronary heart disease; furthermore, distribution of cerebrovascular lesions is greatly affected by race, and Chinese have more intracranial steno-occlusive disease than white. Therefore, it is extremely necessary to update the understanding on incidence, prevalence, cost, outcome, recurrence rate, and treatment strategy for intracranial steno-occlusive disease in China. Unfortunately, we have little knowledge about it so far.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Symptomatic status: as evidenced by TIA or non-severe stroke within the past 12 months attributed to 70% to 99% stenosis of a major intracranial artery (carotid artery, MCA stem [M1], vertebral artery, or basilar artery) are eligible Degree of stenosis: >70% and <99%; stenosis may be diagnosed by TCD, MRA, or CTA to qualify for angiogram performed as part of the study protocol, but must be confirmed by catheter angiography for enrollment in the trial There should 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 infarction related with MCA or BA stenosis Age >=30 years and <=80 years; non-atherosclerotic intracranial lesion will no be included; Expected ability to deliver the stent to the lesion. All the patients should be performed with PTAS beyond a duration of 3 weeks from the latest ischemic symptom onset No fresh 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 measure d 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 Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent.

Exclusion Criteria:

Untoward reaction to anesthesia not able to be overcome by pre-treatment with medications.

Any condition that precludes proper angiographic assessment or makes percutaneous arterial access unsafe.

Tandem extracranial or intracranial stenosis (70-99%) or occlusion that is proximal or distal to the target intracranial lesion Bilateral intracranial vertebral artery stenosis of 70% to 99% and uncertainty about which artery is symptomatic (e.g., if patient has pontine, midbrain, or temporal 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 intracranial stenosis Presence of intraluminal thrombus proximal to or at the target lesion Any aneurysm proximal to or distal to stenotic intracranial artery Intracranial tumor (except meningioma) or any intracranial vascular malformation 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 conversion during the procedure.

Hemorrhagic transformation of an ischemic stroke within the past 15 days. Previous spontaneous intracerebral (parenchymal) or other intracranial (subarachnoid, subdural, or epidural) hemorrhage within 30 days Untreated chronic subdural hematoma >5 mm in thickness Intracranial arterial stenosis related to arterial dissection, moya-moya disease; any known 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 Other cardiac sources of emboli such as left ventricular aneurysm, intracardiac filling defect, cardiomyopathy, aortic or mitral prosthetic heart valve, calcific aortic stenosis, endocarditis, mitral stenosis, atrial septal defect, atrial septal aneurysm, left atrial myxoma MI within previous 30 days Chronic atrial fibrillation; any episode of paroxysmal atrial fibrillation within the past 6 months, or history of paroxysmal atrial fibrillation requiring chronic anticoagulation Intolerance or allergic reaction to any of the study medications, including aspirin, clopidogrel, heparin, nitinol, and local or general anaesthesia History of life-threatening allergy to contrast dye. If not life-threatening and can be effectively pretreated, patient can be enrolled at physicians discretion Recent GI bleed that would interfere with antiplatelet therapy. Active bleeding diathesis or coagulopathy; active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count <125,000, hematocrit <30, Hgb <10 g/dl, uncorrected INR >1.5, bleeding time >1 minute beyond upper limit normal, or heparin-associated thrombocytopenia that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic BP>180 mm hg or diastolic BP>115 mm hg), severe liver impairment (AST or ALT >3 times normal, cirrhosis), creatinine >265.2μmol/l (unless on dialysis) Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment Indication for warfarin or heparin beyond enrollment (note: exceptions allowed for use of systemic heparin during stenting procedure or subcutaneous heparin for deep venous thrombosis prophylaxis while hospitalized) Inability to understand and cooperate with study procedures or provide informed consent.

Severe dementia or psychiatric problem that prevents the patient from following an outpatient program reliably Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study Actively participating in another drug or device trial that has not completed the required protocol follow-up period.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763320

Contacts
Contact: Liqun Jiao, MD 86-10-83198899 ext 8836 jiaoliqun@gmail.com
Contact: Peng Gao, MD 86-10-83198942 gaopengdoc@yahoo.com.cn

Locations
China
Department of neurosurgery, Xuanwu hospital Recruiting
Beijing, China, 100053
Contact: Liqun Jiao, MD    86-10-83198899 ext 8836    jiaoliqun@gmail.com   
Sponsors and Collaborators
Xuanwu Hospital, Beijing
Investigators
Principal Investigator: Feng Ling, MD Xuanwu Hospital, Capital University of Medical Sciences, Beijing, China
  More Information

Publications:

Responsible Party: Xuanwu Hospital, Beijing
ClinicalTrials.gov Identifier: NCT01763320     History of Changes
Other Study ID Numbers: XW125-S002
Study First Received: January 6, 2013
Last Updated: June 4, 2013
Health Authority: China: Ministry of Health

Keywords provided by Xuanwu Hospital, Beijing:
ischemic stroke
intracranial stenting
vascular risk factor management

Additional relevant MeSH terms:
Ischemia
Stroke
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 20, 2014