Fentanyl Administered Intraorally for Rapid Treatment of Orthopedic Pain (FAIRTOP)

Inclusion/Exclusion Criteria. The study population will comprise patients 18-60 years of age who present to the ED with a chief complaint of extremity injury, and who are triaged to the ED's "Minor Surgery" area. The trigger for evaluation for study eligibility will be the clinician-determined need for extremity radiography to rule-out fracture. To participate in the study, patients must meet the following inclusion and exclusion criteria:

• Pediatric patients (age <18) will not be included in the study. There is insufficient evidence for Fentora's safety in this population, even in opioid-tolerant subjects, to justify Fentora's administration to the pediatric population in this first trial of Fentora in the ED setting.
• Older adult patients over 60 years of age will not be included in the study. The clinical experience of the investigators is that fentanyl is more likely to cause respiratory depression in patients in older adults. The selection of 60 years of age as a cutoff is arbitrary, but was chosen to err on the clinically conservative side, and because the age of 60 has been used as a cutoff (for similar reasons of safety) in other trials of opioid analgesia.2 While the added risk to administration of fentanyl in older patients is difficult to quantify, it is noteworthy that one of the drug references commonly used by MGH ED clinicians (UpToDate, www.uptodate.com) states: "Elderly have been found to be twice as sensitive as younger patients to the effects of fentanyl."
• To be included, patients must indicate that their pain is of sufficient severity to warrant treatment with a pain medication stronger than acetaminophen or aspirin. This approach has been utilized with good result in previous clinical trials of analgesia provision in the MGH ED. Allowing potential study subjects to "self-select" (rather than using a predefined pain scale minimum to arbitrarily define "significant pain") has the advantage of empowering potential study subjects. In practice, patient self-selection has not resulted in opioids being administered for what physicians perceive as minimal pain.3,4
• Patients will be excluded from the study if the treating provider judges that IV analgesia is required.
• Patients can only be included in the study if the treating ED provider is aware of, and approves, participation (i.e. participation cannot be allowed to impair provision of standard patient care).
• Patients will be excluded from the study if they have allergy to acetaminophen or to any opiate/opioid.
• Patients will be excluded if they are currently taking phenothiazines (hypotension risk) or CNS depressants (including alcohol), or if they have taken MAO inhibitors (which may potentiate fentanyl's effect) or SSRIs (possible serotonin syndrome) within the past two weeks.
• Patients will be excluded if they have already taken or been administered, opioid analgesia for their current injury. Patients will also be excluded if they are on chronic opioid therapy, or if they (or the medical records) indicate a history of opioid abuse.
• A negative pregnancy test (urine or blood) is required for participation. (Fentanyl is pregnancy category C, with a D categorization for late pregnancy.)
• Breastfeeding mothers will be excluded from the study.
• Patients will be excluded from the study if they are planning to drive home after their ED visit, or if they are judged for any other reason to be non-candidates for opioid therapy.
• The only contraindication to a single-dose of the lansoprazole used as inactive placebo, is known hypersensitivity to the drug. Patients with this hypersensitivity will be excluded from the study.

• Since the Prevacid SoluTab formulation to be used as the inactive placebo contains phenylalanine, subjects with phenylketonuria will be excluded from the study.

  1. Giannoidis P, Furlong A, Macdonald D, et al. Non-union of the femoral diaphysis: The influence of reaming and NSAIDs. J Bone Joint Surg 2000; 82B: 655-658.
  2. Gammaitoni AR, Galer BS, Bulloch S, et al. Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. J Clin Pharmacol. Mar 2003;43(3):296-304.
  3. Thomas SH, Silen W, Cheema F. Effects of morphine analgesia on diagnostic accuracy in ED patients with abdominal pain, J Amer Coll Surg 2003; 196: 18-31.
  4. Thomas SH, Borczuk P, Shackelford J, et al. Patient and physician agreement on abdominal pain severity and need for opioid analgesia. Am J Emerg Med. Oct 1999;17(6):586-590.