Impact of Prophylactic Fentanyl Pectin Nasal Spray on Exercise-Induced Episodic Dyspnea in Cancer Patients: A Double-Blind, Randomized Controlled Trial.

CONTEXT

Episodic breathlessness is common and debilitating in cancer patients.

OBJECTIVES

In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events.

METHODS

In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%-25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1).

RESULTS

Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: -0.9 [95% CI -1.7, -0.1]; T3-T1: -1.3 [95% CI -2.0, -0.5]) and at the end of a 6MWT (T2-T1: -2.0 [95% CI -3.5, -0.6]; T3-T1: -2.3 [95% CI -4.0, -0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI -1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: -1.7 [95% CI -3.3, -0.1]; T3-T1: -2.5 [95% CI -4.2, -0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly.

CONCLUSION

FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs.

TRIAL REGISTRATION

ClinicalTrials.govNCT01832402.