Efficacy of fentanyl buccal tablet and morphine for exertional dyspnoea in patients with cancer: a double-blind, placebo-controlled, randomised clinical trial

Introduction Exertional dyspnoea is highly debilitating. Previous single-dose studies found that prophylactic administration of fentanyl buccal tablet (FBT) improved exertional dyspnoea. In this randomised trial, we compared daily use of prophylactic FBT, oral morphine and placebo on exertional dyspnoea over 14 days. Methods This parallel, double-blind, randomised clinical trial enrolled opioid-tolerant patients with cancer and exertional dyspnoea. After a 5-day observation period, patients were randomised (1:1:1) to receive FBT, morphine or placebo 30 min before daily structured activity for 14 days. Shuttle walk tests (SWTs) were conducted on days 1/5/8/12/15/19. The primary outcome was change in modified Borg Scale dyspnoea intensity during SWTs from day 5 to day 19, analysed using a mixed effects model with treatment, time and treatment×time interaction. SWT distance was a key secondary outcome. Results 67 patients were enrolled and 56 (84%) were randomised. Over the 14-day blinded phase, we observed a significant decrease in the magnitude of dyspnoea intensity change during the SWTs in all three groups, with no significant difference by treatment group (slope change from day 5 to day 19: FBT −2.2 (95% CI −2.9 to –1.6); morphine −1.9 (95% CI −2.7 to –1.2); placebo −2.2 (95% CI −3 to –1.4); time effect p<0.001, treatment×time effect p=0.79). SWT distance increased significantly over time (FBT +93 m; morphine +84 m; placebo +76 m) but did not differ by treatment (p=0.71). Few adverse events were reported. Conclusion All three groups reported less dyspnoea while walking farther; however, no difference was detected between opioids and placebo. These findings should be considered preliminary given the underpowered sample. Trial registration number NCT04188418 .