Morphine for Refractory Dyspnea in Interstitial Lung Disease: A Phase I Study (JORTC-PAL 05)
Morphine for Refractory Dyspnea in Interstitial Lung Disease: A Phase I Study (JORTC-PAL 05)
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DOI：
10.1089/jpm.2018.0272
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发表时间：
2018-12-01
影响因子：
2.8
通讯作者：
Inoue, Yoshikazu
中科院分区：
文献类型：
--
作者：
Matsuda, Yoshinobu;Morita, Tatsuya;Inoue, Yoshikazu
背景：呼吸困难在间质性肺疾病(ILD)患者中很常见，对常规治疗往往难以奏效。关于系统性吗啡在ILD患者中的安全性，人们知之甚少。目的：评价单次皮下注射吗啡的安全性，并确定缓解ILD患者呼吸困难的推荐剂量。设计：我们进行了一项剂量递增的第一阶段研究，以调查单次皮下注射吗啡缓解ILD患者呼吸困难的推荐剂量。地点/对象：符合条件的受试者为ILD住院的静息性呼吸困难患者，他们对传统的呼吸困难治疗无效。1组和2组的吗啡用量分别为1 mg和2 mg。主要终点是剂量限制毒性，它被定义为(1)呼吸抑制，即呼吸频率比基线降低30%，PaCO2增加10Torr；(2)低血压，即全身血压比基线降低20%，并出现与低血压相关的症状；或(3)3级、4级或5级治疗--根据不良事件通用术语标准(版本4)分级的紧急不良事件。结果：共有6名患者入选，其中1组和2组各有3名患者。未观察到剂量限制毒性；3名患者出现更严重的嗜睡，但没有患者经历镇静。结论：2 mg吗啡对ILD患者呼吸困难的耐受性较好，可在进一步的临床试验中进行验证。
Background: Dyspnea is common in interstitial lung disease (ILD) patients and often refractory to conventional treatment. Little is known regarding the safety of systemic morphine in ILD patients. Objective: The objective of this study is to evaluate the safety of a single subcutaneous morphine injection and to determine the recommended dose of morphine for alleviating dyspnea in ILD patients. Design: We conducted a dose-escalation Phase I study for investigating the recommended dose of a single subcutaneous morphine injection to alleviate dyspnea in ILD patients. Setting/Subjects: Eligible subjects were ILD inpatients with dyspnea at rest who were refractory to conventional dyspnea treatment. The morphine doses used were 1 mg and 2 mg in cohort 1 and cohort 2, respectively. The primary endpoint was dose-limiting toxicity, which was defined as (1) respiratory depression, that is, 30% reduction of respiratory rate and 10 Torr increase of PaCO2 compared with baseline; (2) hypotension, that is, 20% reduction of systemic blood pressure compared with baseline and presentation of hypotension-related symptoms; or (3) grade 3, 4, or 5 treatment-emergent adverse events graded by Common Terminology Criteria for Adverse Events (version 4). Results: A total of six patients were enrolled, with three patients each in cohorts 1 and 2. No dose-limiting toxicities were observed; three patients experienced worsened somnolence, but no patients experienced sedation. Conclusion: We conclude that 2 mg of morphine has a tolerable safety profile in ILD patients with dyspnea, and can be tested in further clinical trials.