OXY-1: The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain
Information source: Odense University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Postoperative Pain
Intervention: Oxycodone (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Odense University Hospital Official(s) and/or principal investigator(s): Stine T. Zwisler, Dr., Principal Investigator, Affiliation: University of Southern Denmark
Summary
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.
Clinical Details
Official title: The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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: Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Odense University Hospital, Odense C, Odense DK-5000, Denmark
Additional Information
Starting date: June 2005
Last updated: January 3, 2008
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