ON-LINE APPENDIX: CLINICAL SITES AND STUDY Renji Hospital. Jie-qing Wan, Yao-hua Pan, Yu-ling Fan, Shen- ORGANIZATION hao Ding, Lei Chen Trial Steering Committee Second Affiliated Hospital of Guangzhou Medical University. Wei- Jian-min Liu (Principal Investigator), Bing Leng, Peng Zhang, wen He, Jian-wei Wu, Jian-feng Liang, Sun-ting Jiang Youxiang Li, Jianmin Zhang, Tianxiao Li, Gang Zhu, Chuansheng Liang, Huaizhang Shi, Guobiao Liang, Jieqing Wan, Weiwen He First Hospital of China Medical University. Chuan-sheng Liang, Zhi-feng Wen, Qi-chen Pan, Gang Wang, Hai-long Wang, Xue- Executive Committee bin Shi, Jun-wei Wu, Rui-hua Cai Jianmin Liu, Youxiang Li, Tianxiao Li, Bing Leng, Peng Zhang, Southwest Hospital. Gang Zhu, Zhi Chen, Yin Niu, Hong-ping Guobiao Liang Miu, Wei-hua Tang Clinical Sites in Order of Participants Enrolled Coordinating Center Shanghai Changhai Hospital. Jian-min Liu (Principal Investiga- Qinghai Huang, Bo Hong, Yi Xu, Peng-fei Yang, Yu Zhou tor), Bo Hong, Yi Xu, Qing-hai Huang, Wen-yuan Zhao, Rui Zhao, Peng-fei Yang, Qiang Li, Kai-jun Zhao, Yu Zhou, Chao Data and Safety Monitoring Committee Zou, Yi-bin Fang, Yi-qing Qiu, Guo-sheng Han, Zhi-gang Yang, Dr Yin jian-hua (Chair), Department of Epidemiology, Second Lei Zhang, Qian Zheng, Kai-xia Zhang Military Medical University Dr YaoChen, Institute of Clinical Evaluation affiliated with Tiantan Hospital. You-xiang Li, Xin-jian Yang, Shi-qing Mu, Beijing University Ming Lv, Ai-hua Liu, Peng Jiang, Jing-bo Zhang, Yu-hua Jiang, Dr LinDong, Department of Neurosurgery of Ruijin Hospital, You-ping Zhang Shanghai Jiaotong University, Shanghai, China Henan Provincial People’s Hospital. Tian-xiao Li, Wei-xing Bai, Dr Dong-Lei Song, Department of Neurosurgery of Zhong- Jiang-yu Xue, Zi-liang Wang, Liang fu Zhu, Zhao-shuo Li, Li Li, shan Hospital, Shanghai Fudan University, Shanghai, China Gang-qin Xu, Ying-kun He, Tong-yuan Zhao, Bin Xu Core Laboratory Committee Huashan Hospital. Bing Leng, Yu-xiang Gu, Gong Chen, Bin Xu, Dr Ming-hua Li (chair), Department of Radiology of No.6 Hos- Chao Gao, Qing-zhu An, Yu-jun Liao pital, Shanghai, China Xuanwu Hospital. Peng Zhang, Ming Ye, Xing-long Zhi, Hong-qi Dr Liang Shao, Department of Neurosurgery of No.1 Hospital, Zhang, Chuan He Shanghai, China Dr Li Qiu-ping, Department of Neurosurgery of Zhongshan General Hospital of Shenyang Military. Guo-biao Liang, Zhi- Hospital, Shanghai Fudan University, Shanghai, China qing Li, Xu Gao, Chuang-zhong Li, Jing-yuan Li, Ming-Li Zhao

First Clinical Hospital affiliated with Harbin Medical University. Huai- Statistical and Data Management Center XiaoYan Yan, ChongYa Dong, and Yao Chen, Institute of Clinical zhang Shi, Shan-cai Xu, Bing-jie Zheng, Zhi-yong Ji, Pei Wu, Evaluation affiliated with Beijing University Jing-tao Yuan, Guang Zhang, Chang-ping Jiao, Jian-yi Han Independent Medical Monitor. Yue Chen, GCP ClinPlus Co Second Affiliated Hospital of Zhejiang University. Jian-min Zhang, Jing Xu, Ding-rao Jiang, Xian-yi Chen, Bing Fang, Hua- Publication Committee. Jian-min Liu, Qinghai Huang, Peng-fei qiong Li Yang, Yu Zhou

AJNR Am J Neuroradiol ●:●●2018 www.ajnr.org E1 On-line Table 1: Inclusion and exclusion criteria Inclusion and Exclusion Criteria Inclusion criteria 1) 18–75 years of age, man or nonpregnant woman 2) Unruptured internal carotid artery or vertebral artery saccular aneurysm (including recanalized aneurysms), confirmed by CTA, MRA, or DSA 3) Width of aneurysm neck Ն4 mm and aneurysm size Ն10 mm 4) Parent vessel with a diameter range of 2.0–6.5 mm 5) Indications for Enterprise stent-assisted coiling and Tubridge FD implantation with or without coiling 6) Willing to return to the investigational site for follow-up according to our protocol 7) Understands the nature of the procedure and provision of written informed consent Exclusion criteria 1) No appropriate route to access the aneurysm via endovascular approach 2) An untreated arteriovenous malformation in the territory of the target aneurysm 3) Ruptured aneurysm 4) Anatomy not appropriate for endovascular treatment due to severe intracranial vessel tortuosity or stenosis, or intracranial vasospasm not responsive to medical therapy 5) Major operation within the previous 30 days or planned within the next 90 days after the enrollment date 6) Severe neurologic deficit that renders the patient incapable of living independently (mRS Ն4) 7) Comorbid conditions that may limit survival to Ͻ1yr 8) Enrollment in another trial 9) Poor compliance (inability to complete the full study) 10) Allergy or contraindication for the use of nickel-titanium alloy 11) Inability to receive antiplatelet or anticoagulant medication 12) History of life-threatening allergy to contrast dye

E2 Liu ● 2018 www.ajnr.org On-line Table 2: Number of patients enrolled and treated in site centers Patients Enrolled Full Analysis Set Per-Protocol Set Tubridge Control Tubridge Control Tubridge Control Shanghai Changhai Hospital 22 20 21 16 21 14 Tiantan Hospital 16 20 11 12 10 11 Henan Provincial People’s Hospital 11 11 11 8 10 6 Huashan Hospital 11 16 11 8 10 6 Xuanwu Hospital 6 7 6 3 3 3 General Hospital of Shenyang Military 7 5 7 5 7 5 First Clinical Hospital affiliated with Harbin Medical University 6 4 4 3 3 3 Second Affiliated Hospital of Zhejiang University 6 2 4 2 2 2 Renji Hospital 5 3 4 3 4 1 Second Affiliated Hospital of Guangzhou Medical University 2 1 2 0 2 0 First Hospital of China Medical University 1 1 1 0 1 0 Southwest Hospital 0 2 0 2 0 2 Total 93 92 82 62 73 53

On-line Table 3: Treatment and follow-up details Tubridge Group (n = 79) Enterprise Group (n = 59) Treatment strategy FD alone 21, 26.58% NA FD ϩ loose coiling 58, 73.42% NA Enterprise-assisted coiling NA 59 No. implanted flow diverters 2 Overlapping flow diverters 12 NA Single flow diverter 67 NA Immediate angiographic results Complete occlusion 0, 0.00% 14, 23.73% Neck remnant 4, 5.06% 5, 8.47% Partial occlusion 54, 68.35% 40, 67.80% Disrupted inflow jet and slow flow and flow reduction 21, 26.58% NA 6-Mo follow-up angiographic results Complete occlusiona 55/73, 75.34% 13/53, 24.53% Improvement 14/73, 19.18% 4/53, 7.55% Stable 2/73, 2.74% 4/53, 7.55% Recanalization 2/73, 2.74% 32/53, 60.38% Note:—NA indicates not applicable. a Including 7 parent artery occlusion cases (6 in Tubridge group, 1 in control group).

On-line Table 4: Baseline demographic and clinical characteristic data on randomizationa Patients Quit before Procedure Full Analysis Set Test n =41 n = 144 Method P Value Age (yr) Mean (SD) 53.37 (10.80) 55.64 (10.10) t test .882 Sex ratio (male/female) 6:35 34:110 ␹2 test .218 Medical history Cerebrovascular stroke 3 (7.32%) 17 (11.81%) Fisher exact .572 Coronary artery disease 0 (0%) 5 (3.47%) Fisher exact .588 Hypertension 13 (31.71%) 66 (45.83%) ␹2 test .107 Hypercholesterolemia 1 (2.44%) 7 (4.86%) Fisher exact .687 Diabetes 3 (7.32%) 7 (4.86%) Fisher exact .695 Current or previous smoking 3 (7.32%) 19 (13.19%) Fisher exact .305 Systolic blood pressure (mm Hg) Median 133 (120.00–144.00) 129.50 (120.00–140.00) Wilcoxon .593 Aneurysm location Anterior circulation 41 (100%) 140 (97.28%) Fisher exact .635 Posterior circulation 0 (0%) 4 (2.78%) Aneurysm size (mm) Median 18.00 (13.14–23.95) 17.65 (12.91–25.00) Wilcoxon .888 Aneurysm size classification Large (10–15 mm) 14 (34.15%) 50 (34.72%) ␹2 test .695 Very large or giant (Ͼ15 mm) 27 (65.85%) 94 (65.28%) a Data are No. (%), median (interquartile range), or mean (SD).

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On-line Table 5: A list of all target vessels related to stroke Sex/Age Aneurysm Treatment Cause or mRS at No. (yr) Location Strategy Complication Details Contributing Events last F/U 1 M/49 ICA ophthalmic FD ϩ coils Intraoperative rupture Coil perforation 1 Intraoperative bleeding 2 F/35 ICA cavernous FD ϩ coils SAH after procedure Microwire injury 6 3 F/51 ICA ophthalmic EP ϩ coils Intraoperative rupture Coil perforation 1 4 F/39 ICA ophthalmic FD alone SAH 4 days after procedure Delayed aneurysm rupture 6 Periprocedural bleeding 5 F/47 ICA ophthalmic FD alone SAH 3 days after procedure Delayed aneurysm rupture 6 6 F/44 ICA ophthalmic FD ϩ coils Lateral fissure SAH 1 day postprocedure Unknown, intracranial bleeding not related to 1 aneurysm rupture 7 F/75 ICA ophthalmic EP ϩ coils Intracerebral hematoma 5 hr postprocedure Unknown, intracranial bleeding not related to 6 aneurysm rupture 8 M/43 ICA communicating FD ϩ coils Limb weakness postprocedure Side branch occlusion due to coil introduction 2 Intraoperative ischemia 9 M/55 ICA ophthalmic FD ϩ coils Limb weakness postprocedure Intrastent thrombosis/parent artery occlusion 4 10 F/58 ICA cavernous FD ϩ coils Limb weakness postprocedure Thromboembolic events 3 11 M/52 ICA cavernous EP ϩ coils Limb weakness/speech disorder postprocedure Thromboembolic events 0 12 F/55 ICA cavernous EP ϩ coils Limb weakness postprocedure Thromboembolic events 2 13 F/62 ICA cavernous FD ϩ coils Limb weakness 2 days postprocedure Thromboembolic events 1 Periprocedural ischemia 14 F/58 ICA cavernous FD ϩ coils Limb weakness 2 days postprocedure Thromboembolic events 1 15 F/46 ICA paraclinoid EP ϩ coils Limb numbness 1 day postprocedure Thromboembolic events 1 16 F/48 ICA ophthalmic EP ϩ coils Limb weakness 1 day postprocedure Thromboembolic events 2 17 F/61 ICA ophthalmic EP ϩ coils Limb weakness 1 week postprocedure Thromboembolic events 1 18 F/73 ICA ophthalmic FD ϩ coils Limb weakness/aphasia 1 mo postprocedure Thromboembolic events 1 Delayed ischemia 19 M/67 ICA paraclinoid FD ϩ coils Limb weakness 4 mo postprocedure Parent artery occlusion 0 20 F/67 ICA communicating FD ϩ coils Limb weakness 7 mo postprocedure Parent artery occlusion 2 21 F/61 ICA communicating EP ϩ coils Numbness of limbs 2 mo after procedure Thromboembolic events 1 Note:—EP indicates Enterprise stent; F/U, follow-up. On-line Table 6: A summary of angiographic and clinical outcomes in multicenter prospective studies of flow diverters Complete Complete Aneurysms/ Occlusion Occlusion Neurologic Hemorrhagic Aneurysm Ischemic No. Literature FD Type Subjects at 6 mo Interval at Last F/U at Last F/U Death Stroke Rupture Stroke 1 Byrne et al, 201012 Silk 70/70 NA 9–528 days 24/49 (49%) 4/70 (5.7%) 1/70 (1.4%) 1/70 (1.4%) 2/70 (2.9%) 2 Nelson et al, 2011 (PITA)13 Pipeline 31/31 28/30 (93.3%) 180 days 28/30 (93.3%) 0 1/31 (3.2%) 0 1/31 (3.2%) 3 McAuliffe et al, 201239 Pipeline 57/54 48/56 (85.7%) 6 mo 48/56 (85.7%) 0 0 0 0 4 Kan et al, 201214 Pipeline 58/56 NA 3–5 mo 13/19 (68%) 4/58 (6.9%) 4/58 (6.9%) 3/58 (5.2%) 6/58 (10.3%) 5 Yu et al, 201216 Pipeline 178/143 78/140 (55.7%) 18 mo 49/58 (84%) 3/143 (2.1%) 5/143 (3.5%) 2/143 (1.4%) 1/143 (0.7%) 6 Wakhloo et al, 201515 Surpass 190/165 NA 1 mo; 38 mo; median, 6 mo 118/158 (74.7%) 4/150 (2.7%) 10/150 (6.7%) 1/150 (0.67%) NA 7 Chiu et al, 201517 Pipeline 119/98 93/114 (81.6%) 2ϩ yr 96/103 (93.2%) 1/119 (0.84%) 0/119 (0) 0/119 (0) 5/119 (4.2%) 8 Becske et al, 2017 (PUFS)18,a Pipeline 109/107 81/106 (76.4%) 3 yr 71/76 (93.4%) 3/107 (2.8%) 5/107 (4.7%) 2/107 (2.9%) 4/107 (3.7%) 9 Kallmes et al, 2016 (ASPIRe)10 Pipeline 207/191 33/42 (78.6%) 7.8 mo (mean, 9.7 Ϯ 4.2 mo) 77/103 (74.8%) 3/191 (1.6%) 10/191 (5.2%) 3/191 (1.6%) 9/191 (4.7%) 10 Raymond et al, 2017 (FIAT)8 Pipeline ϩ Silk 75/75 NA 3–12 mo 44/75 (58.7%) 7/75 (9.3%) 3/75 (4%) 2/75 (2.7%) 4/75 (5.3%) 11 Our study (PARAT) Tubridge 82/82 75.3% NA NA 3/82 (3.66%) 5/82 (6.1%) 3/82 (3.66%) 8/82 (9.76%) Note:—F/U indicates follow-up. a Safety data from 6-mo follow-up. JRA Neuroradiol J Am AJNR ● : ●● 08www.ajnr.org 2018 E5