Single-session bronchial thermoplasty for severe asthmatics guided by HXe MRI

HXe MRI 引导下的单次支气管热成形术治疗严重哮喘患者

• 批准号: 8724546
• 负责人: Iulian Constantin Ruset
• 金额: $ 59.07万
• 依托单位: XEMED, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8724546
• 关键词: Accident and Emergency department; Accounting; Aftercare; American; Ancillary Study; Asthma; Biological; Biological Markers; Bronchodilation; Bronchodilator Agents; Bronchoscopy; Cessation of life; Characteristics; Chest; Clinical; Clinical Trials; Companions; Computer software; Control Groups; Data; Data Analyses; Defect; Diagnostic; Diagnostic Imaging; Double-Blind Method; Enrollment; Environmental air flow; FDA approved; Functional Imaging; Goals; Guidelines; Healthcare; Heating; Hospitalization; Image; Image Analysis; Individual; Inferior; Intervention; Life; Link; Lung; MRI Scans; Magnetic Resonance Imaging; Maps; Measures; Methods; Metric; Observational Study; Obstruction; Outcome; Patients; Phase; Pilot Projects; Procedures; Productivity; Publishing; Quality of life; Reader; Recovery; Recruitment Activity; Refractory; Regimen; Risk; Scheme; Sequence Analysis; Series; Severities; Severity of illness; Small Business Innovation Research Grant; Smooth Muscle; Symptoms; Therapeutic; Therapeutic procedure; Thick; Time; TimeLine; Treatment Protocols; Universities; Variant; Visit; Washington; X-Ray Computed Tomography; Xenon; airway obstruction; base; blind; care burden; cost; high risk; image guided therapy; improved; indexing; innovation; minimally invasive; novel; prospective; radiofrequency; respiratory smooth muscle; response; time interval; treatment planning

DESCRIPTION (provided by applicant): Roughly one million Americans with inadequately controlled severe persistent asthma have a particularly high risk of exacerbations, hospitalizations, and death, and account for a per-patient health care burden exceeding $12,000 annually. Bronchial thermoplasty (BT) applies radiofrequency heating to airway smooth muscle reducing its thickness and hyper-reactivity. This novel minimally invasive intervention is applied to all airways 3mm and larger over the course of three procedures. We hypothesize that hyperpolarized xenon (HXe) MRI could identify a subset of dysfunctional airways that dominate the patient's symptoms, and that an image-guided single-session procedure could eliminate overtreatment of non-involved airways, minimize risk and lost productivity, reduce costs of managing this patient group, and convince more payers to reimburse. We propose a double-blind pilot study of thirty patients with severe asthma electing to undergo BT. All patients will participate in three HXe MRI pulmonary functional imaging evaluations of their ventilation defects: at baseline, after their first BT treatment and recovery, and after their final BT treatmet and recovery. Existing and new software methods will identify and rank problematic segmental airways by linking them with the observed ventilation defects. While all patients will receive the full course of BT treatment, half of them will receive a guided BT treatment targeting the most problematic airways in their first treatment session while the control group will receive treatment following the standard sequence. With thirty subjects, this pilot study is adequately powered to detect a change in Quality of Life (QoL) from baseline after one image-guided BT treatment, if changes are similar to published BT trials. We seek, however, greater understanding of biopredictors of BT response from our data. We hypothesize that HXe MRI will provide a metric for grading asthma severity more quantitative than QoL for evaluating BT. An important aim of this study is to evaluate this HXe MRI biomarker for asthma disease severity that includes a set of four images that determine average airway obstruction, bronchodilator reactivity, and variation of these metrics with time. With the HXe MRI metric as our primary endpoint and several asthma QoL indices as secondary end-points, we compare the single session image-guided BT treatment to the standard three-session BT treatment after unblinding the study. Two comparisons are performed: the target group after the single-session guided BT treatment will be compared with the control group after the full three sessions; and will be compared with their own improvement after three sessions, serving as their own controls. If data support the most favorable outcome, that HXe MRI guided BT treatment can reduce overtreatment by two-thirds, cut BT costs in half, and achieve an equivalent benefit, then one million Americans could elect image-guided BT to improve their management of severe asthma. Finally, as a clinically-indicated companion diagnostic for an image-guided therapy, HXe would become an FDA-approved and commercially available diagnostic agent within a few years.

描述（由申请人提供）：大约 100 万患有严重持续性哮喘未得到充分控制的美国人，其病情恶化、住院和死亡的风险特别高，每年每位患者的医疗保健负担超过 12,000 美元。支气管热成形术 (BT) 将射频加热应用于气道平滑肌，减少其厚度和高反应性。这种新颖的微创干预在三个手术过程中适用于所有 3 毫米及更大的气道。我们假设超极化氙 (HXe) MRI 可以识别出主导患者症状的气道功能障碍的子集，并且图像引导的单次手术可以消除对未受影响气道的过度治疗，最大限度地降低风险和生产力损失，降低管理该患者群体的成本，并说服更多付款人报销。 我们提议对 30 名选择接受 BT 的严重哮喘患者进行双盲试点研究。所有患者都将参加对其通气缺陷进行的三项 HXe MRI 肺功能成像评估：基线时、第一次 BT 治疗和恢复后、以及最后一次 BT 治疗和恢复后。现有和新的软件方法将通过将有问题的分段气道与观察到的通气缺陷联系起来来识别和排序有问题的分段气道。虽然所有患者都将接受完整疗程的 BT 治疗，但其中一半患者将在第一次治疗中接受针对问题最严重的气道的指导性 BT 治疗，而对照组将接受治疗 遵循标准顺序。 这项试点研究有 30 名受试者，如果变化与已发表的 BT 试验类似，则有足够的能力检测一次图像引导 BT 治疗后生活质量 (QoL) 较基线的变化。然而，我们寻求从我们的数据中更好地了解 BT 反应的生物预测因子。我们假设 HXe MRI 将提供比 QoL 更定量的哮喘严重程度分级指标来评估 BT。本研究的一个重要目的是评估这种哮喘疾病严重程度的 HXe MRI 生物标志物，其中包括一组四张图像，用于确定平均气道阻塞、支气管扩张剂反应性以及这些指标随时间的变化。 以 HXe MRI 指标作为我们的主要终点，并以几个哮喘 QoL 指数作为次要终点，我们在揭盲研究后将单次图像引导 BT 治疗与标准的三次 BT 治疗进行比较。进行两次比较：单次引导BT治疗后的目标组将在完整的三个疗程后与对照组进行比较；并在三个疗程后与自己的进步进行比较，作为自己的对照。如果数据支持最有利的结果，即 HXe MRI 引导的 BT 治疗可以减少三分之二的过度治疗，将 BT 成本降低一半，并实现同等的效益，那么 100 万美国人可以选择图像引导的 BT 来改善对严重哮喘的管理。最后，作为图像引导治疗的临床指示伴随诊断，HXe 将在几年内成为 FDA 批准的商业化诊断剂。