OXY-1: The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain

The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain

Patients undergoing surgery (thyroidectomy and hysterectomy) will postoperatively receive oxycodone intravenously (IV) as pain management with morphine as an escape medicine, if there is insufficient pain relief with oxycodone. Patients' pain and side effects will be registered and after 24 hours they will answer a questionnaire. All included patients will be genotyped accordingly to CYP2D6 and relevant single nucleotide polymorphisms (SNPs), and measures of plasma levels of oxycodone will be performed.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Oxycodone

Detailed Description

Oxycodone is a semi-synthetic opioid with an analgesic effect in the postoperative pain management comparable to morphine. Oxycodone is N-demethylated by CYP2D6 to its active metabolite oxymorphone, a potent μ-receptor agonist. A genetic polymorphism divides a Caucasian population into two groups: 8% with an enzyme lacking activity, poor metabolizers (PM) and the rest with normal CYP2D6 activity, extensive metabolizers (EM).

Many different, single nucleotide polymorphisms (SNPs) are responsible for interindividual differences in the effect of opioids. Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. P-glycoprotein is responsible for the absorption, excretion and transport of many drugs including opioids over the blood-brain barrier.

The patients will receive the first Oxycodone dosis of 5 mg iv at the end of the surgery. If their pain is not sufficiently relieved they can be given maximum two times Oxycodone 5 mg iv in the recovery room. If still not sufficiently pain relieved they will be given escape medication (Morphine 5 mg iv) until sufficient pain relief.

Further pain treatment will be by Patient Controlled Analgesia (PCA) with bolus doses of Oxycodone 2 mg iv.

During the first 24 hours postoperatively the patients pain and side effects will be registered.

Three blood samples will be drawn: 1. approximately 30 minutes after first Oxycodone dosis, 2. before leaving the recovery room a couple of hours after surgery and 3. 24 hours after surgery. From these samples plasma levels of Oxycodone and its metabolites will be determined and the genotype of CYP2D6 and the above mentioned SNPs will be determined.

The patients will be divided into two groups: Responder and Non-responder. The Responders are characterized by no use of escape medication (morphine) and satisfaction with pain management in final questionnaire. The Non-responders are characterized by use of escape medicine and/or dissatisfaction with pain management in final questionnaire.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Odense
    • Odense C, Odense, Denmark, DK-5000
      • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18-80 years old
• Caucasian race
• Signed informed consent
• Patients admitted for one of the following operations: thyroidectomy, mastectomy, hysterectomy, mammaexpander operation, nasal septum correction and jaw operations.

Exclusion Criteria:

• Allergy towards oxycodone
• Previous daily opioid use
• Known severe illness (terminal cancer, severe dementia, uncompensated heart failure, kidney failure, liver failure and severe lung failure)
• Lack of ability to use patient controlled analgesia or to follow the trial protocol
• Pregnancy
• Severe psychiatric illness
• Alcoholism
• Ongoing treatment with potent CYP2D6 inhibitors (fluoxetine, paroxetine and terbinafine)
• Severe perioperative complications or re-operation within the first 24 hours
• Use of extra pain management during the anaesthesia with an effect after the operation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Responder (satisfaction with pain treatment in questionnaire and no escape medication)
Non-responder (dissatisfaction with pain management in questionnaire and/or escape medication)
Responder status compared to CYP2D6 genotype

Secondary Outcome Measures

Outcome Measure
Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs

Collaborators and Investigators

• Sponsor: Odense University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (ACTUAL): December 1, 2007
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: November 30, 2005
• First Submitted That Met QC Criteria: November 30, 2005
• First Posted (ESTIMATE): December 1, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): January 11, 2008
• Last Update Submitted That Met QC Criteria: January 3, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Oxycodone
• Other Study ID Numbers: EudraCT 2005-001145-42