Yoshinobu Matsuda1,2, Tatsuya Morita3, Tempei Miyaji4, Tomoko Ogawa5, Kuniko Kato6, Takashi Kawaguchi7, Akihiro Tokoro1,2, Satoru Iwase8, Takuhiro Yamaguchi9, Yoshikazu Inoue2. 1. Department of Psychosomatic Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. 2. Clincal Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. 3. Palliative and Supportive Care Division, Seirei Mikatahara General Hospital, Hamamatsu, Japan. 4. Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 5. Department of Pharmacy, National Hospital Organization Osaka National Hospital, Osaka, Japan. 6. Department of Nursing, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. 7. Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. 8. Department of Palliative Medicine, Saitama Medical University, Saitama, Japan. 9. Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
Abstract
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.
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 ILDpatients. 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 ILDpatients. Design: We conducted a dose-escalation Phase I study for investigating the recommended dose of a single subcutaneous morphine injection to alleviate dyspnea in ILDpatients. 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 ILDpatients with dyspnea, and can be tested in further clinical trials.