China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis
Condition: Ischemic Stroke
MeSH terms: Ischemic Stroke
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      Although SAMMPRIS trial has had an impact on the current treatment of intracranial
      atherosclerotic (ICAS), criticism regarding to its design were still raised and remained
      unsettled. In light of SAMMPRIS, medical therapy could not be good as it was; neither
      stenting for ICAD need to be abolished, but rather its role needs to be redefined by future
      prospective trials. Moreover, China is a developing country, and has the world's largest
      population. Since 2010, stroke has been the leading cause of death in China and confers a
      huge burden and effort on patients and health professionals. Compared with western countries,
      ICAS is the most common vascular lesion in patients with cerebro-vascular disease, and is an
      important cause of ischemic stroke and future recurrent events in China. However, its
      treatment strategy and long-term result has not been well determined. The health burden in
      China and ethnic difference of ICAS incidence as well as the willingness to continue clinical
      trials, support the need for ongoing CASSISS in China.

      Pre-CASSISS registry trial:

      A registration pilot trial was performed prior to CASSISS. It aimed to test the credentialing
      of interventionists and participating centers. From July 2013 to Mar 2014, 12 candidates were
      involved in a competitive registration study of recruiting 100 consecutive patients. The
      patients received stenting using Wingspan at each site. As for the candidate centers, the
      following aspects will be considered: stenting experiences, peri-operative complications, and
      the volume of stenting cases. Those met the following criteria were not involved into the
      subsequent randomization trial: 1) each center performed more than 5 procedures; 2) clinical
      results demonstrated the complication rates were more than 15% (stroke or death). At last, 4
      sites were excluded and the remaining 8 were certified and invited for the final
      randomization trial.
    

Intervention name(s): Intracranial stenting group; medical group
Intervention type(s): Procedure; Drug
Intervention description(s): all the participants in this group will be performed with intracranial stenting; 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: ischemic stroke; intracranial stenting; vascular risk factor management