Effect of Prophylactic Fentanyl Buccal Tablet on Episodic Exertional Dyspnea: A Pilot Double-Blind Randomized Controlled Trial

Abstract

Context: Episodic dyspnea is one of the most common, debilitating, and difficult-to-treat symptoms.

Objective: We conducted a pilot study to examine the effect of prophylactic fentanyl buccal tablet (FBT) on exercise-induced dyspnea.

Methods: In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients were asked to complete a six-minute walk test (6MWT) at baseline and then a second 6MWT 30 minutes after a single dose of FBT (equivalent to 20-50% of their total opioid dose) or matching placebo. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the two 6MWTs.

Results: Among 22 patients enrolled, 20 (91%) completed the study. FBT was associated with a significant within-arm reduction in dyspnea NRS between 0 and six minutes (mean change -2.4, 95% CI -3.5, -1.3) and respiratory rate (mean change -2.6, 95% CI -4.7, -0.4). Placebo was also associated with a nonstatistically significant decrease in dyspnea (mean change -1.1). Between-arm comparison of dyspnea scores in the second 6MWT favored FBT, albeit not statistically significant (estimate -0.25, P = 0.068). Global impression revealed more patients in the FBT group than placebo group reporting their dyspnea was at least "somewhat better" in the second 6MWT (4 of 9 vs. 0 of 11, P = 0.03). The other secondary outcomes did not differ significantly between arms.

Conclusions: This study supports that prophylactic FBT was associated with a reduction of exertional dyspnea and was well tolerated. Our findings support the need for larger trials to confirm the therapeutic potential of rapid-onset opioids.

Keywords: Controlled clinical trials; dyspnea; fentanyl; neoplasms; opioid analgesics; physical exertion.

Conflict of interest statement

Conflict of interest disclosure: The authors declare there is no conflict of interest.

Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. CONSORT Diagram

Figure 2. Change in Dyspnea Scores With and Without Study Medications

(A) Without study medications, the two study groups had similar increase in dyspnea with exertion during walk 1. (B) With study medication, both study groups experienced a lower level of increase in dyspnea with exertion during walk 2 compared to the first walk. Patients who received fentanyl buccal tablet had a trend toward greater level of dyspnea relief compared to placebo (estimate -0.25, P=0.068). The error bars represent 95% confidence interval.