The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Responder status compared to CYP2D6 genotype
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
Responder status compared to CYP2D6 genotype
Responder (satisfaction with pain treatment in questionnaire and no escape medication)
Non-responder (dissatisfaction with pain management in questionnaire and/or escape medication)
次要结局
- Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs