BACKGROUND Targeted lung denervation (TLD) is a bronchoscopically delivered ablation therapy that selectively interrupts pulmonary parasympathetic nerve signaling. The procedure has the potential to alter airway smooth muscle tone and reactivity, decrease mucous secretion, and reduce airway inflammation and reflex airway hyperresponsiveness. Secondary outcome analysis of a previous randomized, sham-controlled trial showed a reduction in moderate-to-severe exacerbations in patients with COPD after TLD treatment. A pivotal trial, AIRFLOW-3 has been designed to evaluate the safety and efficacy of TLD combined with optimal medical therapy to reduce moderate or severe exacerbations throughout 1 year, compared with optimal medical therapy alone. METHODS The study design is a multicenter, randomized, full sham bronchoscopy controlled, double-blind trial that will enroll 400 patients (1:1 randomization). Key inclusion criteria are FEV1/FVC < 0.7, FEV1 30 to 60% of predicted, post-bronchodilator, ≥ 2 moderate or 1 severe COPD exacerbations in the prior year, and COPD assessment test (CAT) ≥ 10. Primary objective will be the comparison of moderate or severe COPD exacerbations through 12 months of TLD therapy with optimal medical therapy versus optimal medical therapy alone. The sham group will be allowed to cross over at 1 year. Patients will be followed for up to 5 years. DISCUSSION The multicenter, randomized, full sham bronchoscopy controlled, double-blind AIRFLOW-3 trial will evaluate the efficacy of TLD to reduce moderate or severe COPD exacerbations beyond optimal medical therapy alone. The target population are patients with COPD, who suffer persistent symptoms and exacerbations despite optimal treatment, defining an unmet medical need requiring novel therapeutic solutions. This trial is registered at clinicaltrials.gov: NCT03639051.

中文翻译：

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设计一项多中心，随机，假对照研究，以评估使用Nuvaira®肺神经支配系统治疗慢性阻塞性肺疾病（AIRFLOW-3）后的安全性和有效性。

背景技术靶向肺去神经支配术（TLD）是通过支气管镜递送的消融治疗，其选择性地中断肺副交感神经信号。该手术有可能改变气道平滑肌的张力和反应性，减少粘液分泌，并减少气道炎症和反射性气道高反应性。先前一项随机，假对照试验的二级结果分析显示，接受TLD治疗后COPD患者的中度至重度急性发作减少。一项关键性试验AIRFLOW-3旨在评估TLD与最佳药物治疗相结合的安全性和疗效，与单独使用最佳药物治疗相比，在整个1年中减少中度或重度加重。方法本研究设计为多中心，随机，完全假支气管镜检查，一项双盲试验将招募400名患者（按1：1随机分配）。关键纳入标准为FEV1 / FVC <0.7，FEV1为预测值的30％至60％，支气管扩张剂后，上一年≥2次中度或1次严重COPD急性加重，COPD评估测试（CAT）≥10。最佳药物治疗与仅单独最佳药物治疗的TLD治疗12个月中度或重度COPD恶化的比较。假组将被允许在1年内过渡。将对患者进行长达5年的随访。讨论一项多中心，随机，完全假支气管镜检查对照的双盲AIRFLOW-3试验将评估TLD减轻中度或重度COPD恶化的疗效，而不仅仅是单独的最佳药物治疗。目标人群是患有COPD的患者，尽管进行了最佳治疗，但他们仍然遭受持续的症状和恶化，这定义了未满足的医疗需求，需要新颖的治疗方案。该试验已在Clinicaltrials.gov上注册：NCT03639051。