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

• Published in: Journal of pain and symptom management 2016-10, Vol.52 (4), p.459-468.e1
• Main Authors: Hui, David, MD, MSc, Kilgore, Kelly, BSc, Park, Minjeong, PhD, Williams, Janet, MS, Liu, Diane, MS, Bruera, Eduardo, MD
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Anesthesia & Perioperative Care; Double-Blind Method; Dyspnea; Dyspnea - drug therapy; Dyspnea - etiology; Dyspnea - physiopathology; exercise; Exercise - physiology; Female; Fentanyl - administration & dosage; Fentanyl - adverse effects; Humans; Male; Middle Aged; Nasal Sprays; neoplasms; Neoplasms - complications; Neoplasms - drug therapy; Neoplasms - physiopathology; opioids; Pain Medicine; Pectins - administration & dosage; Pectins - adverse effects; Pilot Projects; randomized controlled trial; Severity of Illness Index; Treatment Outcome; Walk Test
• ISSN: 0885-3924; 1873-6513
• DOI: 10.1016/j.jpainsymman.2016.05.013

Abstract 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 (6MWT) 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% confidence interval [CI] -1.7,-0.1]; T3-T1: -1.3 [95% CI -2.0,-0.5]) and after six minutes (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 +23.8m [95% CI +1.3,+46.2m]; T3-T1: +23.3m [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 6 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.( clinicaltrials.gov registration: NCT01832402)