Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial.

CONTEXT: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined.

OBJECTIVE: We examined the effect of two doses of prophylactic FSS on exertional dyspnea.

METHODS: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35-45% (high dose) or 15-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function.

RESULTS: Thirty of the 50 enrolled patients completed the study. High dose FSS (n=13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P=0.007) and greater walk distance (mean change 44 m; P=0.001) compared to baseline. Low dose FSS (n=17) resulted in a non-significant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P=0.24) and significant increase in walk distance (mean change 24 m; P=0.01) compared to baseline. Global evaluation showed high dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P=0.06). No significant adverse events or detriment to vital signs or neurocognitive function were detected.

CONCLUSIONS: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High dose FSS should be tested in confirmatory trials.