Intranasal Fentanyl versus Placebo for Treatment of Episodic Breathlessness in Hospice Patients with Advanced Non-malignant Diseases.

Abstract Context Episodic breathlessness is a distressing and difficult to treat symptom due to its short duration. Fast actioned intranasal fentanyl is potentially more suitable than oral opioids. Objectives To examine the feasibility, preliminary efficacy and safety of intranasal fentanyl (INF) for the treatment of episodic breathlessness from advanced non-malignant conditions in hospice patients. Methods Phase IIB, double blind, randomized-controlled, multi-site, intranasal fentanyl citrate solution versus placebo cross over feasibility study. Opioid tolerant patients were to treat six episodes of breathlessness using intranasal fentanyl spray. The primary outcome was change in the Visual Analogue Scale for dyspnoea (VAS-D) score from baseline to 15 minutes after study drug's administration (VAS-D15). Other outcomes were to collect demographic data and to determine the use of rescue medications, safety and feasibility of the study design. Results 21 out of 49 eligible patients were enrolled and 19 (90%) patients completed the study. The mean difference in VAS-D15 between fentanyl and placebo was -3.37 mm (95% CI -10.35mm to 3.61 mm, p=0.337). There was no statistically significant or clinically meaningful difference between INF and placebo in relieving the sensation of discomfort in episodic breathlessness. No significant drug related adverse event or detrimental effect on vital signs was observed. Conclusion We found no difference between INF and placebo in relieving episodic breathlessness in non-malignant conditions. INF was well tolerated, and the study design proved to be feasible in hospice patients with advanced diseases. Future study using higher concentration of fentanyl solution may be warranted.