Chronic Administration of Opioids in Cancer Chronic Pain:an Open Prospective Study on Efficacy, Safety and Pharmacogenetic Factors Influence.
试验速览
- 阶段
- 4 期
- 状态
- 暂停
- 发起方
- 入组人数
- 320
- 试验地点
- 6
- 主要终点
- To identify the drug with the best clinical-pharmacological safety-efficacy profile among the four opioids: oral extended-release morphine, oral extended-release oxycodone, transdermal fentanyl and transdermal buprenorphine.
研究概览
简要总结
Aim of this project is to customize the choice of the strong opioid in the treatment of cancer chronic pain through the identification of patient clinical history and pain characteristics, moreover in the analysis the investigators will also correlate the clinical efficacy and safety of opioid treatment with pharmacokinetic and pharmacogenetic patterns in order to identify variables able to predict the efficacy of the treatment or the patient susceptibility towards a specific treatment.
Furthermore with this study the investigators want to identify the pharmacogenomic characterization responsible for pharmacokinetic variability in the conversion between morphine and other opioids, in order to validate the currently available conversion tables from a pharmacokinetic viewpoint, estimating the influence of the most common genetic polymorphisms, and if this characterization could be useful and cost-effective. This study will also focus on the specific clinical-pharmacological response in the elderly and between male and female and on the interactions between opioids and those anticonvulsant and antidepressant drugs routinely used in the pain therapy (study of pharmacovigilance).
详细描述
Pain continues to be a major problem in patients with cancer, affecting 25% to 30% of patients with recently diagnosed cancers. The incidence of pain in advanced stages of cancer approaches 70% to 80%. There are a number of reasons that patients with cancer experience chronic pain either related to the disease itself or to its treatment.
Cancer can spread by metastasis or direct invasion, and 90% of patients with metastasis to osseous structures report pain. Patients with cancer can have neuropathic pain due to direct compression of nerves or plexus or spinal cord involvement.
Inadequate treatment and undertreatment are associated with increased pain scores, decreased functional ability, and increased depression and anxiety.
Opioid administration though proven to be effective still meets with resistance from both healthcare operators, who are seldom willing to prescribe these drugs, and patients, who tend to not take them because of many false beliefs still related to opioids.
It is well demonstrated by the literature that opioids are effective in controlling both acute and chronic pain of nociceptive and/or neuropathic origin. Switching type of opioid and/or administration routes (e.g., from oral to neuraxial) is also known to be an important factor in long-term treatment: appropriate conversion tables elucidating drug equipotence and different potency in base of administration route for the different opioids currently available have therefore been devised and validated in the clinical setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult oncologic patients (>= 18 years old)
- •Chronic peripheral neuropathic and/or nociceptive pain
- •Written informed consent
排除标准
- •Pediatric patients
- •Mental impaired patients
- •Substance abuse disorder
- •Opioid allergy
- •History of opioids use or addiction
- •Severe immunodeficiency, severe renal impairment, severe liver disease
- •Cachectic state
- •HIV positive patients
研究组 & 干预措施
Oral extended-release morphine
干预措施: Morphine (Drug)
Oral extended-release oxycodone
干预措施: Oxycodone (Drug)
Transdermal fentanyl
干预措施: Fentanyl (Drug)
Transdermal buprenorphine
干预措施: Buprenorphine (Drug)
结局指标
主要结局
To identify the drug with the best clinical-pharmacological safety-efficacy profile among the four opioids: oral extended-release morphine, oral extended-release oxycodone, transdermal fentanyl and transdermal buprenorphine.
时间窗: 15 days after randomization (Reduction of at least 40% of median daily pain, on a NRS)
We will define a treatment effective if it will produce a mean reduction of NRS values at least of 40% than basal values. Among all effective treatments, we will identify the best as the one that will have a reduction of NRS to a value of 4 or less in 90% of patients compared to the 70% of the others treatments. To evaluate pharmacological safety the plasma concentrations of the drugs and their metabolites will be measured. We will branch patients population in 3 groups to evaluate the correlation between clinical-pharmacological response and genetics (responder,partially and not responder)
次要结局
- Pharmacokinetic of opioids and of their metabolites during long-term administration; correlation between specific genotypes and clinical response or the clinical/pharmacological susceptibility to side-effects on administration of a specific opioid.(6 months (each patient will be followed for 6 month after enrollment with clinical/pharmacological evaluations once a month and if inefficacy, tolerance or side effects))
研究者
Massimo Allegri
MD
Fondazione IRCCS Policlinico San Matteo di Pavia