A Superiority Trial of Radiofrequency Ablation for Low Back Pain (ASTRAL)

下背痛是导致残疾多年的首要因素，主要由慢性下背痛驱动 (CLBP疼痛持续≥3个月）。减少CLBP社会负担的一个障碍是， 只有很小的治疗效果（功能限制和疼痛改善5-10%）。 腰椎射频消融术（LRFA）是一种微创手术，广泛用于 CLBP。它可用于CLBP孤立于腰椎小关节的患者，定义为疼痛缓解 （“阳性反应”）与对内侧分支神经的局部麻醉内侧分支阻滞（MBB）。LRFA 对这些神经施加热损伤，暂时减少或消除CLBP。与大多数CLBP不同， LRFA可以在精心选择的患者中产生大幅度的改善。然而，LRFA是 神经破坏性，具有潜在的不良影响，并且关于其有效性存在相互矛盾的证据。 虽然一些随机对照试验（RCT）和系统评价支持LRFA的有效性， LRFA的多项RCT显示无显著影响，包括迄今为止最大的RCT。专家们指出， 这些RCT显示没有效果，可能解释为（1）LRFA技术差，不足以充分 病变内侧支，和（2）用于识别LRFA候选者的次优临床选择标准。 LRFA技术和患者选择的最严格循证指南是 脊柱介入学会（SIS）。SIS指南要求技术的各个方面，以优化医疗 CLBP的分支损伤和随之而来的改善。它们还包括严格的临床筛选标准 用于确定适当的LRFA候选者，例如需要≥80%的疼痛改善才能定义阳性 MBB反应，以及2组单独的低麻醉量（<0.5cc）比较MBB。 拟议的研究将涉及一个明确的，双盲多中心的设计和规划， LRFA的RCT与模拟LRFA对照程序的比较：“放射治疗的可靠性试验 下背痛消融术”（ASTRAL）。ASTRAL将遵守SIS指南，解决问题 关于LRFA技术不足和既往RCT的患者选择。以下目标将是 目标1：最终确定统计分析计划（SAP）、研究方案， 操作手册和数据安全性监测计划（DSMP）;目的2：证明临床研究 中心（CRC或“研究中心”）有足够的能力参与未来的ASTRAL RCT，或确定 备用站点。现场要求包括足够的LRFA量、MBB和LRFA的程序标准， 一个研究兼容的环境，和模拟招聘;目标3：准备集中随机化，数据 收集和数据管理;目标4。为未来获得行政和监管批准 多中心ASTRAL RCT;目标5：提交NIAMS U 01合作协议申请以获得资金 未来的RCT

Low back pain is the #1 contributor to years lived with disability, driven mainly by chronic low back pain (CLBP; pain lasting ≥3 months). An obstacle to reducing the societal burden of CLBP is that most treatments have only small magnitude treatment effects (5-10% improvements in functional limitations and pain). Lumbar radiofrequency ablation (LRFA) is a minimally invasive procedure that is widely performed for CLBP. It can be used in patients for whom CLBP is isolated to the lumbar facet joints, defined by pain relief (“positive responses”) with local anesthetic medial branch blocks (MBBs) to the medial branch nerves. LRFA applies a thermal lesion to these nerves, temporarily reducing or eliminating CLBP. Unlike most CLBP treatments, LRFA can result in large-magnitude improvements in well-selected patients. However, LRFA is neurodestructive, has potential adverse effects, and there is conflicting evidence regarding its effectiveness. While some randomized controlled trials (RCTs) and systematic reviews support the effectiveness of LRFA, multiple RCTs of LRFA show no significant effects, including the largest RCT to date. Experts have noted that those RCTs showing no effects may be explained by (1) poor LRFA technique insufficient to adequately lesion the medial branches, and (2) suboptimal clinical selection criteria for identifying LRFA candidates. The most stringent evidence-based guidelines for LRFA technique and patient selection are those of the Spine Intervention Society (SIS). The SIS guidelines mandate various aspects of technique to optimize medial branch lesioning and consequent improvements in CLBP. They also include stringent clinical screening criteria for determining appropriate LRFA candidates, such as requiring ≥80% pain improvement to define positive MBB responses, and 2 separate sets of comparative MBBs with low anesthetic volume (<0.5cc). The proposed research will involve the design and planning of a definitive, double-blind multicenter RCT of LRFA compared to a simulated LRFA control procedure: “A Superiority Trial of Radiofrequency Ablation for Low Back Pain” (ASTRAL). ASTRAL will adhere to the SIS guidelines, addressing concerns regarding inadequate LRFA technique and patient selection of past RCTs. The following Aims will be addressed over a 1.5-year funding period: Aim 1: Finalize the statistical analysis plan (SAP), study protocol, manual of operations, and data safety monitoring plan (DSMP); Aim 2: Demonstrate that the clinical research centers (CRCs or “sites”) have sufficient capacity for participation in the future ASTRAL RCT, or identify alternate sites. Site requirements include sufficient LRFA volume, procedural standards for MBBs and LRFAs, a research-compatible environment, and mock recruitment; Aim 3: Prepare for centralized randomization, data collection, and data management; Aim 4. Obtain administrative and regulatory approvals for the future multicenter ASTRAL RCT; Aim 5: Submit a NIAMS U01 Cooperative Agreement application to obtain funding for the future RCT.