Fentanyl or Morphine for Persistent Dyspnea in COPD: a multicenter randomised cross-over trial

One of the most prevalent and impactful symptoms in COPD is persistent dyspnea, occurring in the majority of patient with advanced COPD. Opioids, mostly morphine, have been investigated and suggested as treatment in palliative care guidelines. However, in recent years multiple trials on morphine for persistent dyspnea have shown no clinical benefit, and there are concerns regarding adverse events. Transdermal fentanyl has not yet been investigated for this indication. We performed a multicenter, cross-over, double-dummy RCT, investigating transdermal fentanyl (12 mcg·h −1 ), morphine (10 mg p.o. bid), and placebo, during three treatment periods of two weeks (including three days wash out). Patients with persistent dyspnea despite optimal therapy and mMRC score≥3 caused by COPD, FEV 1 <50%, and stable disease were included. The primary endpoint was change in mean daily dyspnea score on a numeric rating scale (NRS). Secondary outcomes were change in worst daily dyspnea (NRS), health status (CCQ), anxiety (HADS-A), hypercapnia (capillary bloodgas), mastery (CRQ-M), and sleep quality (NRS). Between April 2019 and November 2024, 59 randomisations were performed in 58 participants (69±7 years, 54% female, FEV 1 33±10%), 37 participants completed the study. The main reasons for study discontinuation were exacerbations (n=13) and side effects (n=7). There were no significant differences between both fentanyl and morphine compared to placebo for mean and worst dyspnea, sleep, health status, mastery, anxiety, hypercapnia, or side effects (except for a possible difference in vomiting). This study demonstrated no positive effect of transdermal fentanyl nor oral morphine, compared to placebo in the treatment of persistent dyspnea in COPD.