ColonoscopyPhase 4AbstralNCT01604187
Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients
A Phase 4 study testing Fentanyl in people with Colonoscopy and Pain, run by Turku University Hospital at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Colonoscopy, Pain
- What is being tested?
- Fentanyl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 1 siteFinland
- Study dates
- Apr 2012to 30 Apr 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ASA I-III
- Colonoscopy
- Written informed consent from participating subject
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Colonoscopy, Pain
- Being tested
- Fentanyl, Placebo
- Keywords
- sublingual fentanyl, pain in coloscopy, The efficacy and safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FentanylDrug
Ten minutes before the procedure fentanyl sublingual tablet (Abstral ® 100 µg, ProStrakan) will be given to the patient.
PlaceboDrug
Ten minutes before the procedure placebo sublingual tablet will be given to the patient.
| Study group | Role | What they receive |
|---|---|---|
| Fentanyl | Active comparator | Ten minutes before the procedure fentanyl 100 mikrograms sublingual tablet will be given to the patient. Receives: Drug: Fentanyl |
| Placebo | Placebo comparator | Ten minutes before the procedure placebo sublingual tablet will be given to the patient. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
Anxiety will be measured using NRS (0 = no anxiety, 10=maximal anxiety). Pain will be monitored by using numercal rating scale NRS (0-10), sedation by using NRS (0-10, 0= not sedated at all, 10=no response) . Nurse's and surgeon's satisfaction with the procedure will be evaluated using NRS (0-10). Adverse effects of opioids will be evaluated by patients using NRS (0-10)) for the following items: drowsiness (alert / very drowsy), pleasantness (very unpleasant / very pleasant feeling) and nausea/vomiting (no nausea / very strong nausea). In addition, all other adverse effects will be recorded.
Secondary outcomes (1)
The safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
SpO2 and breath rate will be followed throughout the procedure. If the peripheral arterial oxygen saturation decreases below 90 % or breath rate falls below 8 per min, additional oxygen will be given. In case of excess opioid effects, naloxon 0.1mg iv will will be given.
The patients will be interviewed by telephone on the first day after the procedure approximately 24 hours later and.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2012 (estimated)
- Study startApr 2012
- Primary completion22 Apr 2019
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ColonoscopyStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Mari Fihlman, Turku University Hospital
- Investigators
- Klaus T Olkkola, professor, Principal investigator, Turku University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01604187
- Sponsor's protocol ID
- Abstral
- Acronym
- Abstral
- Status last verified
- Sep 2019
- First submitted
- 21 May 2012
- Last updated
- 11 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Procedural Pain Treatment With Transmucosal Sublingual Fentanyl Tablet in Colonoscopy Patients
- ClinicalTrials.gov ID
- NCT01604187
- Acronym / sponsor ID
- Abstral / Abstral
- Conditions
- Colonoscopy, Pain
- Keywords
- sublingual fentanyl, pain in coloscopy, The efficacy and safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Study start
- Apr 2012
- Primary completion
- 22 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 23 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fentanyl | Active comparator | Drug: FentanylTen minutes before the procedure fentanyl 100 mikrograms sublingual tablet will be given to the patient. |
| Placebo | Placebo comparator | Drug: PlaceboTen minutes before the procedure placebo sublingual tablet will be given to the patient. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ASA I-III
- Colonoscopy
- Written informed consent from participating subject
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FentanylTen minutes before the procedure fentanyl sublingual tablet (Abstral ® 100 µg, ProStrakan) will be given to the patient. | Drug | Fentanyl |
| PlaceboTen minutes before the procedure placebo sublingual tablet will be given to the patient. | Drug | Placebo |
Primary outcome
Efficacy of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
Anxiety will be measured using NRS (0 = no anxiety, 10=maximal anxiety). Pain will be monitored by using numercal rating scale NRS (0-10), sedation by using NRS (0-10, 0= not sedated at all, 10=no response) . Nurse's and surgeon's satisfaction with the procedure will be evaluated using NRS (0-10). Adverse effects of opioids will be evaluated by patients using NRS (0-10)) for the following items: drowsiness (alert / very drowsy), pleasantness (very unpleasant / very pleasant feeling) and nausea/vomiting (no nausea / very strong nausea). In addition, all other adverse effects will be recorded.
1 secondary outcome
The safety of fentanyl transmucosal tablet to placebo in patients having colonoscopy.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klaus T Olkkola, professor principal investigator
Turku University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fentanyl in people with Colonoscopy and Pain, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of fentanyl transmucosal tablet to placebo in patients having colonoscopy.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2019.