Efficacy and Safety of Rapid-Onset Opioids for Exertional Dyspnea in Cancer Patients

速效阿片类药物治疗癌症患者劳力性呼吸困难的疗效和安全性

• 批准号: 10062496
• 负责人: David Hui
• 金额: $ 45.07万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062496
• 关键词: Address; Adverse effects; Affect; Anatomy; Bathing; Breakthrough Pain; Cancer Patient; Clinical Trials; Common Terminology Criteria for Adverse Events; Data; Data Set; Dimensions; Distress; Dose; Dyspnea; Dyspnea Management; Emergency department visit; Exertion; Fentanyl; Formulation; Goals; Home; Home environment; Hospitalization; Informed Consent; Intervention; Malignant Neoplasms; Meta-Analysis; Mission; Morphine Sulfate; Neurocognitive; Opioid; Outcome; Outcome Measure; Oxygen; Pain; Patient Care; Patient Monitoring; Patient Outcomes Assessments; Patients; Pattern; Pharmaceutical Preparations; Physiological; Placebo Effect; Placebos; Prophylactic treatment; Public Health; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Research; Research Design; Safety; Series; Symptoms; System; Testing; Titrations; United States Food and Drug Administration; United States National Institutes of Health; Walking; arm; associated symptom; cancer pain; comparative efficacy; confirmatory trial; cost; daily functioning; effective therapy; efficacy evaluation; evidence base; experience; functional outcomes; improved; improved functioning; innovation; insight; instrument; novel; novel therapeutics; opiate tolerance; opioid epidemic; opioid use; patient population; patient tolerability; prevent; primary endpoint; prophylactic; response

PROJECT SUMMARY Dyspnea is one of the most common and distressing symptoms associated with cancer, occurring in up to 70% of patients. The vast majority of patients with dyspnea experience frequent episodes of breathlessness triggered by daily activities, such as walking and bathing. Understandably, dyspnea with exertion can significantly limit patients' daily function and negatively impact their quality of life. If uncontrolled, these highly distressing dyspnea episodes can result in costly emergency room visits and hospitalizations. Because exertional dyspnea is under- researched, few effective treatment options are available. The long-term goal of our group's research is to develop effective, evidence-based therapies for dyspnea in patients with cancer. Exertional dyspnea is particularly difficult to treat because of its rapid onset, short duration, and high intensity. This raises the possibility that rapid-onset opioids that are currently approved for breakthrough cancer pain may be effective as prophylactic treatment to reduce exertional dyspnea and maximize function. On the basis of our preliminary data from recent clinical trials, we hypothesize that fentanyl sublingual spray (FSS) is effective in relieving exertional dyspnea. The overall objective of the proposed 3-arm, double-dummy, parallel- group randomized clinical trial is to compare the efficacy of FSS, morphine sulfate, and placebo in exertional dyspnea. The primary specific aim of this study is to compare the effect of prophylactic FSS, morphine sulfate, and placebo on the intensity of exertional dyspnea at the end of a shuttle walk test (SWT). In the second specific aim, we will compare their effects on SWT distance, average daily dyspnea, personalized daily activity, symptom burden, and quality of life. The third aim is to explore their effects on neurocognitive function, addictive potential, adverse effects, and pattern of opioid use. After obtaining written informed consent, we will monitor patients closely on usual opioids for 5 days before randomly assigning them to receive FSS, morphine sulfate, or placebo prophylactically once daily for 14 days. The proposed study is innovative in that the indications (i.e., exertional dyspnea and prophylactic management), intervention (i.e. FSS, proportionally dosed), patient population (i.e., patients with cancer), patient-reported outcome measures (e.g. personalized dyspnea activity, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events instrument, and Drug effects Questionnaire), and study design (i.e. home setting) that it will address are novel. The expected outcome of the proposed study is that FSS will be established as a treatment option for exertional dyspnea in patients with cancer while a rich dataset will be provided on the neurocognitive effects and addictive potential of opioids to inform safe opioid use during this era of opioid crisis. Successful completion of this adequately powered trial will have a positive effect on patient care by alleviating the intensity of exertional dyspnea, enhancing patients' ability to function in their daily lives, and improving the quality of life of these highly distressed patients.

项目摘要 呼吸困难是与癌症相关的最常见和令人痛苦的症状之一，最多发生在70％ 患者。绝大多数呼吸困难的患者经常触发呼吸困难的经常发作 通过日常活动，例如步行和洗澡。可以理解的是，用劳累呼吸困难可以显着限制 患者的日常功能，并对他们的生活质量产生负面影响。如果不受控制，这些高度令人痛苦的呼吸困难 发作可能会导致昂贵的急诊室就诊和住院。因为劳累呼吸困难不足 经过研究，几乎没有有效的治疗选择。 我们小组研究的长期目标是为呼吸困难开发有效的，基于证据的疗法 癌症患者。劳累呼吸困难特别难以治疗，因为它的发作迅速，持续时间短， 和高强度。这增加了当前批准突破的快速发作的阿片类药物的可能性 癌症疼痛可能是预防性治疗的有效，可减少劳累呼吸困难并最大化功能。在 我们最近临床试验的初步数据的基础，我们假设芬太尼舌下喷雾（FSS） 有效缓解劳累呼吸困难。拟议的3臂，双人，平行的总体目标 组随机临床试验是比较FSS，吗啡硫酸吗啡和安慰剂在劳累中的疗效 呼吸困难。这项研究的主要特定目的是比较预防性FSS，吗啡硫酸吗啡， 安慰剂在穿梭步行测试结束时施加呼吸困难的强度（SWT）。在第二个特定 目的，我们将比较它们对SWT距离，平均每日呼吸困难，个性化日常活动，症状的影响 负担和生活质量。第三个目的是探索它们对神经认知功能的影响，上瘾的潜力， 不良影响和阿片类药物使用的模式。获得书面知情同意书后，我们将监视患者 紧密接近通常的阿片类药物5天，然后随机分配它们以接受FSS，吗啡硫酸盐或安慰剂 每天进行预防一次，持续14天。 拟议的研究具有创新性，因为这些适应症（即劳累呼吸困难和预防性 管理），干预（即FSS，按比例服用），患者人群（即癌症患者）， 患者报告的结果指标（例如个性化呼吸困难活动，患者报告的结果版本 不良事件工具的常见术语标准和药物效应问卷）和研究 它将解决的设计（即家庭环境）是新颖的。拟议的研究的预期结果是FSS 将作为癌症患者的劳累呼吸困难的治疗选择确定，而丰富的数据集将 在此期间提供有关阿片类药物的神经认知作用和上瘾的潜力，以告知阿片类药物的使用。 阿片类药物危机时代。成功完成此足够动力试验将对患者产生积极影响 通过减轻劳累性呼吸困难的强度来护理，增强患者在日常生活中的功能， 并改善这些高度困扰的患者的生活质量。