China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis "CASSISS"

Recruiting

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Intracranial stenting group Procedure
    Other Names: Intracranial stenting group
    Intervention Desc: all the participants in this group will be performed with intracranial stenting
    ARM 1: Kind: Experimental
    Label: Intracranial stenting group
    Description: all the participants in this group will be performed with intracranial stenting
  • Medical group Drug
    Other Names: medical group
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: medical group
    Description: 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

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary 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 up to 30 days Yes
Secondary the number of participants who suffer from disabling stroke or death beyond 30 days through 36 months No
Secondary the number of participants who suffer from restenosis (>50%) related to intracranial stenting up to 36 months No
Secondary the number of participants who suffer from any stroke, severe transient ischemic attack (TIA), cardiovascular events related to intracranial stenting or medical therapy up to 36 months No
Secondary the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index at 7 days, 30 days, 6 months, 12 months, 24 months and 36 months No
Secondary the number of participants who survives in both groups beyond 12 months to 36 months No
Primary stroke or death within 30 days after enrollment up to 30 days Yes
Primary any stroke, death in the territory of the symptomatic intracranial artery beyond 30 days through 12 months beyond 30 days to 12 months No

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