Zecca, E., Brunelli, C., Centurioni, F., Manzoni, A., Pigni, A., & Caraceni, A. (2017). Fentanyl sublingual tablets versus subcutaneous morphine for the management of severe cancer pain episodes in patients receiving opioid treatment: A double-blind, randomized, noninferiority trial. Journal of Clinical Oncology, 35, 759–765.
To directly compare fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) in the first 30 minutes of a severe breakthrough pain episode.
Patients were randomly assigned to receive FST or SCM. Placebo was saline solution or a sublingual tablet reproducing the fentanyl preparation. Re-medication was available after 30 minutes for patients who did not achieve at least a 2-point reduction in pain. Average pain scores were obtained at baseline, 10, 20, 30, and 60 minutes. SCM was given at a 5 mg dose, and the dose for FST was 100 mcg. A non-inferiority margin of 1 point on the pain scale was used.
Double-blind, double dummy, noninferiority RCT
Numeric rating scale
Overall there was no significant difference in change of pain intensity between groups; however, non-inferiority of FST was not shown because the difference between groups was less than the margin established for testing. Patients tended to prefer the tablet rather than subcutaneous injection.
Subcutaneous morphine showed slightly better efficacy than the fentanyl tablet for reducing breakthrough pain intensity. Both approaches were effective.
Risk of bias (no blinding)
This study showed that both fentanyl sublingual tablets and subcutaneous morphine were effective in reducing the intensity of breakthrough pain. Findings here showed slightly better efficacy of the subcutaneous morphine, though patients preferred the tablet.