Clinical trial NCT01358500: An Assessment of Fentanyl Dose Requirements in Opioid-maintained Individuals
Official title: An Assessment of Fentanyl Dose Requirements in Opioid-maintained Individuals
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Opioid Dependence
Keywords: opioid dependence
tolerant
dependent
Lead sponsor: University of Adelaide
Sponsor class: OTHER
First posted: 2011-05-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study seeks to determine the suitable doses of fentanyl with acceptable adverse effect and safety profile in opioid-dependent patients. The investigators anticipate that a well tolerated dose of fentanyl which produces demonstrable analgesia will be found and will be related to the patient's maintenance opioid dose.

Detailed description: Fentanyl is a synthetic opiate with a (clinical) potency of 50 to 100 times that of morphine. Because of its high lipid solubility, fentanyl has a rapid onset of action and a relatively short duration of action. Fentanyl is one of the most widely used agents in the synthetic opioids family. Being a pure agonist with no active metabolites, it is highly suitable for use in patients with opioid tolerance. It can be used outside of an intensive-care clinical environment.

Evidence-based guidelines for clinicians on which agents to use, what doses should be considered and whether treatment doses are related to the dose and the pharmacological properties of the maintenance opioid are lacking, but needed. This study seeks to determine the suitable doses of fentanyl required in opioid-tolerant patients, which are able to overcome the tolerance and hyperalgesia while maintaining an acceptable therapeutic index. The importance of this study is that it has the potential to improve acute pain management in the opioid-tolerant population.

Eligibility criteria: Inclusion Criteria:

1. Male or female, aged 18 to 65.
2. Maintained on any opioid with oral morphine equivalent daily dose (MEDD) of 60 mg and above.
3. Have adequate intravenous access for drug infusion.
4. Are currently abstaining from oral and intravenous recreational drug use.

Exclusion Criteria:

1. Known positive for Hepatitis B, Hepatitis C or HIV
2. Contraindication to cold pain testing e.g. cardiac or vascular disease especially Raynaud's phenomenon, blood pressure problems, diabetes, epilepsy and recent serious injury.
3. Using medication which affects pupil size e.g. glaucoma
4. Visual acuity poorer than 6 / 25 corrected (so that saccadic eye movements can be performed correctly.
5. Patients with respiratory insufficiency and poor respiratory drive. The criteria will be a spirometry reading of less than 70% the predicted value and/or having resting oxygen saturation levels of less than 95% on air.
6. Subject is pregnant and/or lactating.
7. Chronic use of benzodiazepines which cannot be withheld for 5 half-lives of the benzodiazepine the patient is on.
8. Known intolerance to fentanyl or other opioids
9. Patients taking tramadol.
10. Patients taking CYP3A4 inhibitors like amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, diltiazem, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine, selective serotonin reuptake inhibitors (SSRIs) and tacrolimus.
11. A positive urine test for benzodiazepines on the day of screening or testing.
12. A positive breathalyzer test on the day of testing.
13. Creatinine clearance \< 30ml/min as estimated by Cockcroft-Gault formula.
14. Patients with bradyarrythmia.

Primary outcomes:
measure: Attainment of analgesia
timeFrame: Within 2 hours after starting the infusion
Secondary outcomes:
measure: Pupillometry
timeFrame: Within 2 hours after infusion starts
measure: Saccadic eye movement
timeFrame: Within 2 hours after infusion starts
measure: Morphine Benzedrine Group Scale
timeFrame: Within 2 hours after infusion starts
measure: Electroencephalography (EEG)
timeFrame: Within 2 hours after infusion starts
measure: Subjective Opioid Withdrawal Scale
timeFrame: Within 1 hour after infusion stops
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: PARC, Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: University of Adelaide
name: Paul E Rolan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lotsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Pain Symptom Manage. 2005 May;29(5 Suppl):S90-103. doi: 10.1016/j.jpainsymman.2005.01.012.
citation: Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology. 2004 Jul;101(1):212-27. doi: 10.1097/00000542-200407000-00032. No abstract available.