Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients
Condition: Colonoscopy; Pain
MeSH terms: Pain, Procedural
Study type: Interventional
Phase: Phase 4

Summary: 
      Colonoscopy is generally considered an invasive procedure that causes remarkable pain to the
      patient. The pain associated with the procedure is not caused by the insertion of the scope
      but from inflating of the colon in order to do the inspection. It has been shown that
      colonoscopy can be performed successfully without sedation (Leung, 2010), but many patients
      feel discomfort during the procedure. Factors predicting a painful colonoscopy are
      female-gender, degree of patient nervousness and the technical difficulty of the colonoscopy
      (Ylinen et al. 2009). Also age under 40, previous abdominal surgery and use of sedation are
      associated with painful colonoscopy ( Seip et al. 2009). Most often sedation and/or analgesia
      are achieved by administering a benzodiazepine or a combination of a benzodiazepine and an
      opioid (Fanti et al. 2009, Maskelar et al. 2009,), dexmedetomidine (Dere et al. 2009) or by
      using non-pharmacologic methods (Amer-Cuenca et al. 2011). Tramadol as monotherapy did not
      significantly decrease pain intensity or endoscopist's evaluation of colonoscopy (Grossi et
      al. 2004). Currently, intravenous midazolam is the drug used most commonly to introduce some
      sedation for colonoscopy. Intravenous sedation definitely increases the cost of procedure;
      drug administration, need for pulse oximetry monitoring and the need for follow-up after the
      procedure make colonoscopy sometimes expensive and troublesome. It has also been shown, that
      low-dose midazolam neither relieves discomfort nor makes patients forget it (Elphick et al.
      2009).

      Fentanyl is a short-acting opioid widely used in anesthesia management. Transmucosal
      sublingual formulation of fentanyl has been developed to further improve the management of
      pain. When administered as a sublingual fast-dissolving tablet (Abstral®) that is placed
      under the tongue, the effects is fast and predictable. Its active ingredient is absorbed by
      the body through the mucous membrane. After administration of buccal fentanyl maximum plasma
      drug concentration was measured after 25 minutes (Darwish et al. 2011). Plasma fentanyl
      concentrations versus time following buccal and sublingual administration are very similar
      (Darwish et al. 2008). Abstral® sublingual tablets should be administered directly under the
      tongue at the deepest part. Sublingual administration is an easy and non-invasive method of
      pain treatment for the patient coming to colonoscopy done as an office based procedure. Other
      advantages compared to invasive methods are improved comfort of patients and no need for
      intravenous access because of pain relief. Before, it has been used in the management of
      breakthrough pain in cancer patients. Sublingual fentanyl is shown to be effective and
      well-tolerated for the treatment of breakthrough cancer pain (Uberall et al. 2011). The use
      of transmucosal tablet for colonoscopy patients is a quite new approach.
    

Detailed description: 
      The purpose of this study is to evaluate the efficacy of fentanyl transmucosal tablet to
      placebo in patients having colonoscopy.

      Fentanyl is a highly lipophilic drug absorbed very rapidly through the oral mucosa and more
      slowly through the gastrointestinal tract. Orally administered fentanyl undergoes pronounced
      hepatic and intestinal first pass effects.

      Abstral® is a quick dissolving sublingual tablet formulation. Rapid absorption of fentanyl
      occurs over about 30 minutes following administration of Abstral®. The bioavailability of
      Abstral® has not been studied but is estimated to be about 70%. Mean maximal plasma
      concentrations of fentanyl range from 0.2 to 1.3 ng/ml (after administration of 100 to 800 µg
      Abstral®) and are reached within 22.5 to 240 minutes.

      Fentanyl is metabolised primarily via CYP3A4 to a number of pharmacologically inactive
      metabolites, including norfentanyl. Within 72 hours of intravenous fentanyl administration
      around 75% of the dose is excreted into the urine, mostly as metabolites, with less than 10%
      as unchanged drug. About 9% of the dose is recovered in the faeces, primarily as metabolites.
      Total plasma clearance of fentanyl is about 0.5 l/h/kg. After Abstral® administration, the
      main elimination half-life of fentanyl is about 7 hours (range 3-12.5 hours) and the terminal
      half-life is about 20 hours (range 11.5-25 hours). Impaired hepatic or renal function could
      cause increased serum concentrations. Elderly, cachectic or generally impaired patients may
      have a lower fentanyl clearance, which could cause a longer terminal half-life for the
      compound.

      This is a randomized controlled double-blind study. A total of 200 patients will be included.
      The patients are recruited from 18-85 year old male or female patients undergoing
      colonoscopy. In view of previous studies (Amer-Cuenca et al. 2011) it can be calculated that
      87 patients will be needed per group to demonstrate a 30% decrease in the worst experienced
      pain at a level of significance P = 0.05 and power of 90%. Because of possible dropouts, 100
      patients will be recruited to both groups. Pain will be assessed by numeral rating scale
      (NRS). For the calculation of the sample size, coefficient of variation is assumed to be 70%
      in both groups.
    

Intervention name(s): Fentanyl; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ten minutes before the procedure fentanyl sublingual tablet (Abstral ® 100 µg, ProStrakan) will be given to the patient.; Ten minutes before the procedure placebo sublingual tablet will be given to the patient.
Intervention MeSH terms: Fentanyl
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: sublingual fentanyl; pain in coloscopy; The efficacy and safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.