Official Title: “Fentanyl Administered Intraorally for Rapid Treatment of Orthopedic Pain in the ED”

Assess whether transbuccal fentanyl provides more rapid relief of orthopedic pain, than does the comparator Percocet

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Placebo Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

Patients will be initially deemed eligible for study consideration if, after MGH ED nursing triage, an X-ray is ordered for suspected isolated extremity injury and the triage acuity level is "Minor". Study staff (physicians) will monitor the ED registration and triage areas to assess whether triaged patients are potentially eligible. For ED patients with minor isolated injuries, X-rays are often ordered from triage, where there is a supervising physician (or nurse practitioner) available to examine patients and direct care. Either at triage (for patients undergoing care at that location) or when patients are moved to the ED's Minor Surgery area, the supervising healthcare provider will be approached immediately after that individual's evaluation of the patient, and before any pain medication is administered, to begin the process of eligibility ascertainment.

If the provider agrees that the patient may be a candidate for the study, the next step will be for the provider to ask the patient if study staff may approach to discuss the trial. If the patient agrees to have study staff approach to discuss the trial, study personnel (all EM resident or Attending-level physicians) will be introduced by healthcare providers to potential subjects. Study staff will then converse with the patients about the study's aims, methodology, and risks, confirming eligibility and determining if patients will consent to participate.

Patients who are approached, but who are determined to be ineligible, will have no data recorded, other than their age and race/ethnicity and the reason they were ineligible. If eligible patients provide written consent in the manner and form dictated by Partners guidelines, the study procedures will commence.

For eligible patients who do not give consent, study physicians will emphasize that patient care will be unaffected by their decision. No further contact will occur between study staff and those patients. No identifying information about such patients will be recorded, but their age and race/ethnicity will be recorded. (Recording this information will allow for subsequent assessment for selection bias, and will also help search for patterns in patient types refusing analgesia trial participation.)

The actual medication administration will involve the following steps:

1. Patients participating in the study will be identified and placed in a "room" (stretcher or actual ED room) in the MGH ED's Minor Multipurpose (MIMP) area;

2. RNs will obtain the study medication pairs (buccal tablet + oral tablet) from the computerized medication storage area - RNs will take the next-numbered medication pair from the MGH Research Pharmacy-prepared drug packaging;

3. Actual medications will be administered by a licensed physician (a study co-investigator, EM resident or Attending physician at MGH), who is not the co-investigator monitoring the patient for endpoint assessment - the physician administering the medication/placebo will inform neither the patient nor the clinical or study staff, the identity of the medication/placebo pair given. Patients will be monitored by a study physician co-investigator physically present with the patient, for a total of 120 minutes after administration of medication. They will be asked q-5-minutes, through 60 minutes, to rate their pain and degree of nausea, as well as to describe any adverse reactions to the medication. Both pain and nausea levels will be recorded using 10-point scales. Use of such scales is common in the pain literature, and is an emerging tool for evaluation of nausea.1,2 Data collection for analgesia efficacy will cease after 60 minutes, but patients will be monitored for at least another 60 minutes to maximize safety; patients will be assessed for discharge suitability by treating clinicians/nurses in the same fashion as other ED patients who receive opioids.

Vital signs (respiratory rate, blood pressure, heart rate, pulse oximetry) will be monitored for the two hours of the study. Continuous pulse oximetry will be used during the first study hour, and q5-minute spot-check pulse oximetry will be used during the second study hour; pulse oximetry monitoring will be changed to continuous mode during the second study hour if any spot-check reading falls below 98%. Other (non-pulse oximetry) vital signs will be monitored q5-minutes during the first study hour, and q15-minutes during the second study hour. These vital signs monitoring parameters represent the minimum for study subjects; treating clinicians or study staff physicians can increase the frequency of vital signs monitoring at their discretion. Any study subject not admitted to the hospital, will be discharged under the care of a responsible adult.

At the conclusion of the data collection period, patients will be asked if they would want to receive the same medication in the future. Other than a 24-hour telephone call (made only if patients agree), intended to assess for delayed problems such as nausea/vomiting, there will be no other study procedures or interventions.

1. Bijur PE, Latimer CT, Gallagher EJ. Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department.

Academic Emergency Medicine. 2003;10(4):390-392.

2. Warden C. Prehospital use of ondansetron reduces nausea and episodes of vomiting in adults and children over 12 years old [abstract]. Prehosp Emerg Care. 2007;11:132.

Intervention(s) in this Clinical Trial

• Drug: Fentanyl rapid dissolving tablet 100mcg
  • Fentanyl rapid dissolving tablet 100mcg will be given
• Drug: lansoprazole 15mg rapidly dissolving tablet + Percocet PO
  • lansoprazole 15mg rapidly dissolving tablet + Percocet PO will be given

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Subject receives placebo swallowed pill, and Fentora 100mcg rapidly dissolving transbuccal tablet
• Active Comparator: 2
  • Subject receives Percocet swallowed pill, and Prevacid comparator rapidly dissolving transbuccal tablet

Primary Measures

• Time to analgesia
  • Time Frame: 60 minutes
    Safety Issue?: No

Secondary Measures

• Occurrence of untoward opioid side effects
  • Time Frame: 120 minutes
    Safety Issue?: Yes

• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Massachusetts General Hospital

Overall Clinical Trial Officials and Contacts

Stephen H Thomas, MD, MPH Principal Investigator Massachusetts General Hospital  

Overall Contact: Stephen H Thomas, MD MPH 617-726-7622 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00685295

Study ID Number: FAIRTOP

ClinicalTrials.gov Identifier: NCT00685295

Health Authority: United States: Food and Drug Administration