A Comparison of Analgesic and Respiratory Effects From Tapentadol Versus Oxycodone After Laparoscopic Hysterectomy.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Pain 1 hour postoperatively.
研究概览
简要总结
Opioids remain the first-line drugs for the treatment of moderate to severe postoperative pain, but the use is limited by well-known side-effects, most of which are dose-dependent.
The opioid oxycodone is standard therapeutic treatment for acute postoperative pain, either in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®. Oxycodone provides analgesic effects through µ-opioid receptors in the central nervous system.
Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong analgesic with a dual mechanism of action on µ-opioid receptors and noradrenaline reuptake in the central nervous system. Tapentadol is an active compound, devoid of active metabolites and not reliant on enzyme systems. For these reasons, it has a low drug interaction potential. This dual mechanism also translates clinically into less adverse effects than with pure opioid agonists like oxycodone. This is probably due to less µ-opioid receptor stimulation.
Tapentadol has been shown effective in models of acute, osteoarthritic, neuropathic and cancer pain. There is now an increasing use of tapentadol in postoperative pain treatment in Norway. However, there is a lack of broad-based evidence for the use of tapentadol in the post-surgical setting. So far, to our knowledge, there are only published studies on postoperative pain treatment after orthopedic and dental surgery, but none related to deep abdominal pain.
Tapentadol is shown in several studies on chronic pain patients to have comparable analgesic effects to traditional opioid pain medications like oxycodone and morphine, but with a more tolerable side-effect profile. In the postoperative setting after dental or orthopedic surgery, studies have shown less nausea and constipation. It has also been suggested a lower frequency of pruritus compared with oxycodone, but no difference in central nervous system symptoms such as sleepiness or dizziness. The most dangerous side-effect from opioids is respiratory depression with the potential of fatal outcome. The investigators have not found any publications from short-term postoperative pain management comparing the respiratory effect of tapentadol to the traditional opioids.
The aim of the study is to compare the analgesic effect and side-effects of this new analgesic, tapentadol, to the standard treatment to day, oxycodone, in the acute postoperative period after hysterectomy.
详细描述
Postoperative pain is a major cause of postoperative suffering, prolonged hospitalization, complications and increased costs. It has been shown that postoperative pain is a frequent and unresolved problem in Norwegian hospitals, and so also internationally. Building knowledge on pain prophylaxis and treatment of postoperative pain is an area with substantial potential for improvement and affecting many patients.
Opioids remain as first-line drugs for the treatment of moderate to severe postoperative pain, but the use is limited by well-known side-effects, most of which are dose-dependent.
The opioid oxycodone is used as standard therapeutic treatment for acute postoperative pain, either in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®. Oxycodone is a pure opioid receptor agonist with central and peripheral effects.
Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong analgesic with a dual mechanism of action. It is a µ-opioid receptor agonist with central and peripheral effects, and it also inhibits noradrenaline reuptake in the central nervous system. Tapentadol is an active compound, devoid of active metabolites and not reliant on enzyme systems. For these reasons, it has a low drug interaction potential.
Opioid receptors are usually not well expressed in non-inflamed peripheral tissue and they have limited effect on the peripheral pathophysiology and origin of acute wound pain. While postoperative pain basically is induced by relevant nociceptive pain nerve stimulation, there is also a neuropathic component in most cases. Opioids are not very effective in blocking neuropathic pain in low to moderate doses. Also, opioids do not have the potential to block the wind-up of pain when given before the start of surgical trauma. The noradrenaline re-uptake inhibition (NRI) component of tapentadol is believed to have effect on descending pathways in the spinal cord. Such excitatory and inhibitory pathways act through monoamine systems mediated by noradrenaline and 5-hydroxytryptamine (5-HT). The inhibition of noradrenaline reuptake increases monoaminergic transmission in the descending pain inhibitory pathways, leading to reduced pain sensation. It seems like tapentadol produce not simply additive, but synergistic anti-nociceptive action by inhibitory actions in µ-opioid receptor agonism and NRI. While the effect on µ-opioid receptors is important in nociceptive pain, the NRI component seems to be especially relevant for both acute and persistent neuropathic pain.
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
- Double (Investigator, Outcomes Assessor)
盲法说明
Patients were not told which medicine they were given, but due to difference in apperance of pills they would be able to find out which medicine they were given if they wanted to. Care providers at the hospital ward administering the medication would know which medicine were given due to apperance.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women diagnosed with a benign gynecological condition, undergoing laparoscopic, supra-cervical or total hysterectomy in general anesthesia.
- •Age 18-64 years.
- •ASA (American Society of Anesthesiologists) classification I-III.
- •Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonisation GCP, and national/local regulations.
- •The patients will be recruited from the patient population at the Department of Gynaecology.
排除标准
- •Age under 18 or over
- •BMI > 31 and/or weight <55 kg, >85 kg.
- •Chronic pain syndromes related to organ systems other than the female reproductive system.
- •Chronic opioid therapy (codeine medication allowed up to 60 mg/day) or enteral steroid therapy.
- •Alcohol or medical abuse/addiction.
- •Chronic obstructive pulmonary disease (spirometry with postbronchodilator FEV1/FVC ratio less than 0.7), untreated asthma (FEV1/FVC is reduced to less than 0.70), obstructive sleep apnea or other conditions known to predispose for respiratory depression.
- •Neurological diagnosis with affection of respiratory system or prone to seizures.
- •Previously diagnosed kidney (glomerular filtration rate <60 mL/min/1.73 m2 over 3 months) or liver impairment (ALAT > 45 U/L; ASAT > 35 U/L; ALP > 105 U/L; GT > 45 U/L age 18-39 or GT > 75 U/L age over 39; LD > 205 U/L).
- •Biliary tract disease.
- •Paralytic ileus.
- •Heart failure (NYHA III-IV).
- •Malignancy of any kind under treatment. Malignancy during last 5 years.
- •HIV infection. Infections of any kind affecting the patient's clinical status, i.e. upper or lower airway infection, urinary tract infection, deep wound infection. Infections not affecting the patient's clinical status, i.e. conjunctivitis, is not an exclusion criteria.
- •Untreated depression, severe anxiety or other psychiatric disorders independent of treatment.
- •Nursing mothers.
- •Cognitive failure, language barriers, hearing/visual disability or other factors which make follow-up difficult.
- •Allergy or contraindication to any of the medications used in the study.
- •Lactose intolerance.
- •Monoamine oxidase inhibitors or SNRI (serotonin norepinephrine reuptake inhibitors) within 14 days prior to randomization. SSRI (selective serotonin reuptake inhibitors) use is not an exclusion criterion if stable dose for at least 30 days before screening.
- •H1-antihistamine is not an exclusion criterion unless the patient experiences somnolence as a side-effect.
- •The concurrent use of benzodiazepines, barbiturates, neuroleptics, phenytoin tricyclic antidepressants, gabapentinoids, tramadol, clonidine, cimetidine, rifampicin, protease inhibitors, St John's wort (Hypericum perforatum), macrolides and antimycotics such as ketoconazole and fluconazole is not allowed.
- •Known complications to anesthesia or difficult airway (Definition of difficult airway: "The clinical situation in which a conventionally trained anesthesiologist experiences difficulty with mask ventilation, difficulty with tracheal intubation, or both.").
- •Patients who have participated in other clinical trials during the last 6 months are excluded to avoid confounders to the current study and for patient safety reasons.
研究组 & 干预措施
Oxycodone
Active comparator drug administrated.
干预措施: Oxycodone (Drug)
Tapentadol
Experimental drug administrated.
干预措施: Tapentadol (Drug)
结局指标
主要结局
Pain 1 hour postoperatively.
时间窗: 1 hour
Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone.
次要结局
- Pain 2 hours postoperatively.(2 hours)
- Pain 3 hours postoperatively.(3 hours)
- Pain 24 hours postoperatively.(24 hours)
- Pain relief 30 minutes(30 minutes)
- Pain relief 2 hours(2 hours)
- Pain relief 1 hour(1 hours)
- Pain relief 3 hours(3 hours)
- Pain relief 24 hours(24 hours)
- Global medication performance(24 hours)
- Time to first rescue medicine(24 hours)
- Total rescue analgesic consumption(24 hours)
- Respiratory depression(24 hours)
- Respiratory rate(24 hours)
研究者
Harald Lenz
Principal investigator
Oslo University Hospital