An Assessment of Fentanyl Dose Requirements in Opioid-maintained Individuals

Opioid Dependence Clinical Trial

— FEN001  

Official title:

An Assessment of Fentanyl Dose Requirements in Opioid-maintained Individuals

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01358500
• Other study ID #: FEN001
• Status: Recruiting
• Phase: N/A
• First received: May 20, 2011
• Last updated: February 4, 2013
• Start date: February 2012
• Est. completion date: May 2013

Study information

• Verified date: February 2013
• Source: University of Adelaide
• Contact: Paul E Rolan
• Phone: +61882222712
• Is FDA regulated: No
• Health authority: Australia: National Health and Medical Research Council
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: May 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Opioid Dependence
• Opioid-Related Disorders

Intervention

Drug:
• Fentanyl
Intravenous infusion using STANPUMP

Locations

Country	Name	City	State
Australia	PARC, Royal Adelaide Hospital	Adelaide	South Australia

Sponsors (1)

Lead Sponsor	Collaborator
University of Adelaide

Country where clinical trial is conducted

Australia, 

References & Publications (2)

Lötsch J. Pharmacokinetic-pharmacodynamic modeling of opioids. J Pain Symptom Manage. 2005 May;29(5 Suppl):S90-103. Review. — View Citation

Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology. 2004 Jul;101(1):212-27. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Attainment of analgesia	Attainment of analgesia as evidenced by having the cold pain tolerance test reading to twice the baseline value or reaching the absolute value of 2 minutes.	Within 2 hours after starting the infusion	No
Secondary	Pupillometry	The pupil diameter will be measured every 30 minutes during the infusion.	Within 2 hours after infusion starts	Yes
Secondary	Saccadic eye movement	The average peak velocity of the saccadic eye movement will be measured every half an hour for 2 hours.	Within 2 hours after infusion starts	No
Secondary	Morphine Benzedrine Group Scale	This paper test will take 3 minutes to complete and will measure the degree of euphoria.	Within 2 hours after infusion starts	Yes
Secondary	Electroencephalography (EEG)	The delta, theta and alpha Fz-Cz and Pz-Oz activity will be measured every 30 minutes during the infusion.	Within 2 hours after infusion starts	No
Secondary	Subjective Opioid Withdrawal Scale	This paper test will take 3 minutes to complete and will measure the degree of withdrawal. It will be done at 15, 30 and 60 minutes post infusion.	Within 1 hour after infusion stops	Yes