Morphine or Fentanyl for Refractory Dyspnea in COPD: a multicenter, cross-over RCT

Introduction and aim Refractory dyspnea is a common symptom in advanced COPD, with a high negative impact. As treatment for refractory dyspnea, opioids -mostly morphine- have been investigated and made their way into palliative care guidelines. But in recent years there have been multiple negative studies in COPD. Furthermore, there is no RCT investigating transdermal fentanyl. We aimed to investigate whether both morphine and fentanyl are more effective than placebo for refractory dyspnea in COPD. <bold>Methods:</bold> This was a multicenter, cross-over, dubbel-dummy RCT, investigating fentanyl (patch,12mcg/hr), morphine (10 mg p.o. bid) and placebo, during 3 periods of 2 weeks (incl. 3 days wash out). Patients with stable COPD, FEV1<50%, and mMRC score≥3 with refractory dyspnea caused by COPD despite optimal therapy were included. <bold>Results:</bold> Between 2019 and 2024, 59 participants were included (69±7 years, 54% female, FEV1 33±10%), of which 37 completed all three study periods. The main reasons for discontinuation were exacerbations (n=13) and side effects (n=7). There were no significant differences between both fentanyl and morphine compared to placebo with respect to mean and worst dyspnea, sleep quality, health-related quality of life, mastery, anxiety or capillary blood gas analysis (table 1). <bold>Conclusion:</bold> This study demonstrated no positive effect of both morphine and fentanyl compared to placebo in the treatment of refractory dyspnea in COPD. <fig><object-id>erj;66/suppl_69/OA1188/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>