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

基本信息

批准号：
10318991
负责人：
David Hui
金额：
$ 44.16万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
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/10318991
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

项目摘要

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.

项目概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，发生率高达 70% 的患者。绝大多数呼吸困难患者都会经历频繁的呼吸困难发作通过日常活动，例如散步和洗澡。可以理解的是，用力时呼吸困难会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。如果不加以控制，这些非常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治疗。因为劳力性呼吸困难是低经过研究，几乎没有有效的治疗方案。我们小组研究的长期目标是开发有效的、基于证据的治疗呼吸困难的方法癌症患者。劳力性呼吸困难由于发病快、持续时间短、治疗起来特别困难。和高强度。这增加了目前获批突破性的速效阿片类药物的可能性癌症疼痛作为预防性治疗可能有效减少劳力性呼吸困难并最大限度地提高功能。在根据我们最近临床试验的初步数据，我们假设芬太尼舌下喷雾剂（FSS）可有效缓解劳力性呼吸困难。所提议的 3 臂、双虚拟、并联的总体目标分组随机临床试验旨在比较 FSS、硫酸吗啡和安慰剂在运动中的疗效呼吸困难。本研究的主要具体目的是比较预防性 FSS、硫酸吗啡、安慰剂对穿梭步行测试（SWT）结束时劳力性呼吸困难的强度进行影响。在第二个具体目标，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。第三个目标是探索它们对神经认知功能、成瘾潜力、不良反应以及阿片类药物的使用模式。获得书面知情同意书后，我们将监测患者密切使用常用阿片类药物 5 天，然后随机分配他们接受 FSS、硫酸吗啡或安慰剂预防性每天一次，持续 14 天。拟议的研究具有创新性，因为适应症（即劳力性呼吸困难和预防性呼吸困难）管理）、干预（即 FSS，按比例剂量）、患者群体（即癌症患者）、患者报告的结果测量（例如个性化呼吸困难活动、患者报告的结果版本不良事件通用术语标准工具和药物影响问卷），以及研究它将涉及的设计（即家居环境）是新颖的。拟议研究的预期结果是 FSS 将被建立为癌症患者劳力性呼吸困难的治疗选择，同时丰富的数据集将提供有关阿片类药物的神经认知作用和成瘾潜力的信息，以便在此期间安全使用阿片类药物阿片类药物危机时代。成功完成这项动力充足的试验将对患者产生积极影响通过减轻劳力性呼吸困难的强度、增强患者的日常生活能力来进行护理，并改善这些高度痛苦的患者的生活质量。