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）：大约一百万的美国人患有不足的严重持续性哮喘的美国人患有加重，住院和死亡的风险特别高，并且每年的医疗保健负担超过12,000美元。支气管热成形术（BT）将射频加热施加到气道平滑肌，以降低其厚度和过度反应性。在三个程序的过程中，这种新颖的微创干预措施适用于所有3mm和更大的气道。我们假设超极化氙（HXE）MRI可以识别出主导患者症状的功能失调的气道子集，并且图像引导的单程程序可以消除过度治疗的非涉及气道，使风险和损失的生产力最小化，降低该患者组的成本，并降低了该患者群体的成本，并为更多的付款人提供了更多的付款者。 我们提出了一项双盲试点研究，对三十例重哮喘的患者选择接受BT。所有患者将参与三个HXE MRI肺功能成像评估其通风缺陷：在基线，第一次BT治疗和恢复后以及最终的BT处理和恢复之后。现有和新的软件方法将通过将其与观察到的通风缺陷联系起来来识别和对有问题的节段气道进行排名。虽然所有患者都将接受BT治疗的完整课程，但其中一半将在第一次治疗中接受针对最有问题的气道的指导性BT治疗，而对照组将接受治疗 遵循标准序列。 有了30名受试者，该试点研究就足够的动力来检测一种与已发表的BT试验相似的图像引导BT处理后基线的生活质量变化（QOL）。但是，我们从我们的数据中寻求对BT响应的生物记者的更多了解。我们假设HXE MRI将为评估BT提供比QOL更定量的分级哮喘严重性的度量。这项研究的一个重要目的是评估该HXE MRI生物标志物的哮喘疾病严重程度，其中包括一组四个图像，这些图像决定了平均气道阻塞，支气管扩张剂的反应性以及这些指标随时间的变化。 以HXE MRI指标为我们的主要终点，几个哮喘QOL指数为次要终点，我们将单个会话图像引导的BT处理与未闪烁研究后的标准三局BT处理进行了比较。进行了两次比较：在整个三个课程后，将与对照组进行单课导后的BT处理后的目标组；并将在三个课程后与自己的改进进行比较，并作为自己的控制。如果数据支持最有利的结果，那么HXE MRI指导的BT治疗可以减少过度治疗三分之二，将BT成本降低了一半，并获得了同等的收益，那么一百万的美国人可以选择图像指导的BT来改善他们对严重哮喘的管理。最后，作为图像引导疗法的临床指示伴侣诊断，HXE将在几年内成为FDA批准的诊断剂。