Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients
Information source: Turku University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Colonoscopy; Pain
Intervention: Fentanyl (Drug); Placebo (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Turku University Hospital Official(s) and/or principal investigator(s): Klaus T Olkkola, professor, Principal Investigator, Affiliation: Turku University Hospital
Overall contact: Mari Fihlman, MD, Phone: 02-3144061, Email: mari.fihlman@tyks.fi
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.
Clinical Details
Official title: Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Efficacy of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
Secondary outcome: The safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- ASA I-III
- Colonoscopy
- Written informed consent from participating subject
Exclusion Criteria:
- A previous history of intolerance to the study drug or related compounds and
additives
- History of alcoholism, drug abuse, psychiatric, psychological or other emotional
problems that are likely to invalidate informed consent
- Sleep apnoea
- Chronic obstructive pulmonary disease
- BMI ≥ 35 or weight < 50 kg
- SpO2 < 90 %
- Concomitant drug therapy known to cause significant enzyme induction or inhibition of
CYP 3A4.
- Pregnancy or nursing.
Locations and Contacts
Mari Fihlman, MD, Phone: 02-3144061, Email: mari.fihlman@tyks.fi
Turku University Hospital, Turku 20521, Finland; Recruiting Mari Fihlman, MD, Phone: 02-3144061, Email: mari.fihlman@tyks.fi
Additional Information
Starting date: April 2012
Last updated: November 19, 2014
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