Kim Kee D, Lee K Stuart, Coric Domagoj, Chang Jason J, Harrop James S, Theodore Nicholas, Toselli Richard M
1Department of Neurological Surgery, UC Davis, Sacramento, California.
2Division of Neurosurgery, Vidant Health, Greenville, North Carolina.
J Neurosurg Spine. 2021 Feb 5;34(5):808-817. doi: 10.3171/2020.8.SPINE191507. Print 2021 May 1.
The aim of this study was to evaluate whether the investigational Neuro-Spinal Scaffold (NSS), a highly porous bioresorbable polymer device, demonstrates probable benefit for safety and neurological recovery in patients with complete (AIS grade A) T2-12 spinal cord injury (SCI) when implanted ≤ 96 hours postinjury.
This was a prospective, open-label, multicenter, single-arm study in patients with a visible contusion on MRI. The NSS was implanted into the epicenter of the postirrigation intramedullary spinal cord contusion cavity with the intention of providing structural support to the injured spinal cord parenchyma. The primary efficacy endpoint was the proportion of patients who had an improvement of ≥ 1 AIS grade (i.e., conversion from complete paraplegia to incomplete paraplegia) at the 6-month follow-up visit. A preset objective performance criterion established for the study was defined as an AIS grade conversion rate of ≥ 25%. Secondary endpoints included change in neurological level of injury (NLI). This analysis reports on data through 6-month follow-up assessments.
Nineteen patients underwent NSS implantation. There were 3 early withdrawals due to death, which were all determined by investigators to be unrelated to the NSS or the implantation procedure. Seven of 16 patients (43.8%) who completed the 6-month follow-up visit had conversion of neurological status (AIS grade A to grade B [n = 5] or C [n = 2]). Five patients showed improvement in NLI of 1 to 2 levels compared with preimplantation assessment, 3 patients showed no change, and 8 patients showed deterioration of 1 to 4 levels. There were no unanticipated or serious adverse device effects or serious adverse events related to the NSS or the implantation procedure as determined by investigators.
In this first-in-human study, implantation of the NSS within the spinal cord appeared to be safe in the setting of surgical decompression and stabilization for complete (AIS grade A) thoracic SCI. It was associated with a 6-month AIS grade conversion rate that exceeded historical controls. The INSPIRE study data demonstrate that the potential benefits of the NSS outweigh the risks in this patient population and support further clinical investigation in a randomized controlled trial. Clinical trial registration no.: NCT02138110 (clinicaltrials.gov).
本研究旨在评估研究性神经脊髓支架（NSS），一种高度多孔的可生物吸收聚合物装置，在损伤后≤96小时植入时，对于完全性（美国脊髓损伤协会损伤分级A 级）T2 - 12脊髓损伤（SCI）患者的安全性和神经功能恢复是否具有可能的益处。
这是一项针对MRI显示有明显挫伤的患者的前瞻性、开放标签、多中心、单臂研究。将NSS植入冲洗后的脊髓髓内挫伤腔的中心，旨在为受损的脊髓实质提供结构支持。主要疗效终点是在6个月随访时美国脊髓损伤协会损伤分级提高≥1级（即从完全性截瘫转变为不完全性截瘫）的患者比例。为该研究设定的预设客观性能标准定义为美国脊髓损伤协会损伤分级转化率≥25%。次要终点包括损伤神经平面（NLI）的变化。本分析报告了6个月随访评估的数据。
19例患者接受了NSS植入。有3例因死亡而早期退出，研究者均判定这些死亡与NSS或植入手术无关。完成6个月随访的16例患者中有7例（43.8%）神经状态发生转变（美国脊髓损伤协会损伤分级从A级转变为B级[n = 5]或C级[n = 2]）。与植入前评估相比，5例患者的损伤神经平面改善了1至2个节段，3例患者无变化，8例患者恶化了1至4个节段。研究者判定，未出现与NSS或植入手术相关的意外或严重器械不良影响或严重不良事件。
在这项首次人体研究中，在对完全性（美国脊髓损伤协会损伤分级A级）胸段SCI进行手术减压和稳定的情况下，将NSS植入脊髓内似乎是安全的。其6个月的美国脊髓损伤协会损伤分级转化率超过了历史对照。INSPIRE研究数据表明，在该患者群体中，NSS的潜在益处大于风险，并支持在随机对照试验中进行进一步的临床研究。临床试验注册号：NCT02138110（clinicaltrials.gov）。
