Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Chronic pelvic pain
研究概览
简要总结
The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping.
详细描述
Endometriosis is a chronic inflammatory disease affecting approximately 10% of reproductive-aged women. Severe pain symptoms and subfertility result in a lower quality of life, higher prevalence of depression and loss of productivity. Consequently, the economic impact of endometriosis is high. Treatment options to suppress chronic pain symptoms in patients with (deep) endometriosis are inadequate, resulting in increased opioid consumption. Ketamine (in our study we will use the S-enantiomer, esketamine), is a versatile drug with analgesic, anti-inflammatory and antidepressant effects and is commonly used in the treatment of chronic pain patients and has shown promising outcomes. However, whilst esketamine targets multiple aspects of endometriosis simultaneously (pain, inflammation, depression), studies on esketamine as treatment for chronic pain due to endometriosis have never been reported. Therefore we aim to conduct a randomized controlled trial to assess the efficacy of esketamine infusion versus placebo in the treatment of chronic endometriosis-induced 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
- Triple (Participant, Care Provider, Investigator)
盲法说明
The researchers and participants will not be informed on the nature of the treatment until the trial is fully completed, and the database is locked. Only the clinical pharmacist who prepares the study medication will be aware of the treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •All pre-menopausal women aged above 18 years
- •Diagnosed with endometriosis (ultrasound, MRI or previous laparoscopic and/or diagnostic surgery) according to the #Enzian classification [52]. This means that endometriosis is present in the following compartments:
- •Rectovaginal space (minimal A1) and/or
- •Sacrouterine ligaments, cardinal ligaments, pelvic sidewall (minimal B1) and/or
- •Rectum (minimal C1) and/or
- •Endometriosis of the intestines, diaphragm and/or
- •Adenomyosis (according to the morphological uterus sonographic assessment (MUSA) or evident adenomyosis on the MRI) [53, 54] and/or
- •Peritoneal / superficial endometriosis (diagnosed laparoscopically and not treated during surgery).
- •Mild to severe chronic pelvic pain (NRS scale >= 6). The 11-point NRS scale ranges from '0' representing no pain to '10' representing the worst pain imaginable.
- •Resistant to current recommended lines of analgesics (paracetamol, NSAIDs)
- •Usage of strong opioids must not have been prescribed or otherwise have been discontinued for more than 1 week.
- •An indication for endometriosis resection surgery or on the waiting list for surgical treatment
- •Ability to understand the patient information letter and to give oral and written informed consent
- •No alteration in the utilization of hormonal therapy ≤1 months prior to inclusion.
排除标准
- •Pain score <6 out of 10 (NRS) for chronic pelvic pain
- •Endometriosis affecting the bladder and ureter
- •Increased intracranial pressure
- •Poorly regulated hypertension, >180/100mmHg at rest
- •Patients with thyroid disease
- •Patients with cancer
- •History of psychiatric illness (schizophrenia, psychosis, delirium, manic depression)
- •Serious medical disease (e.g., cardiovascular, renal , pulmonary or liver disease)
- •Severe liver disease
- •Patients with glaucoma
- •Usage of strong opioid medication
- •Usage of xanthine derivatives or ergometrine
- •Unstable angina, heart failure, history of cerebral vascular accident (CVA)
- •Patients suffering from an active infection
- •Patients with epilepsy
- •Patients trying to achieve pregnancy and or patients who are breastfeeding
- •Not being able to answer questionnaires (in Dutch)
- •Mentally incompetent (patients not able to make decisions that are in their best interests, this will be evaluated by their treating physician (e.g. patients with an intellectual disability or mental retardation))
- •Alcohol or drug abuse
- •Patient with a known (es)ketamine allergy
- •Abnormal liver enzyme levels at baseline (ASAT, ALAT, GGT, AF, Bilirubin total)
- •Patients are allowed to continue the following pain medications: paracetamol, non-steroidal anti-inflammatory drugs as described previously by Sigtermans et al. (Trial NL466 (NTR507))* according to their stable use in dose and frequency.
- •*in case of tramadol, amitriptylin, selective serotonin reuptake-inhibitors, gabapentin and pregabalin, the usage may also be continued during this study.
研究组 & 干预措施
Esketamine
Esketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour).
干预措施: Esketamine hydrochloride (Drug)
Placebo
8 hours infusion with saline (NaCl 0.9%)
干预措施: Placebo (Drug)
结局指标
主要结局
Chronic pelvic pain
时间窗: 4 weeks after the 8 hour infusion treatment.
The effect of treatment allocation on the NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
次要结局
- Depressive symptoms(Baseline, 4 weeks after infusion treatment)
- Dysmenorrhea(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Dyschezia(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Dysuria(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Dyspareunia(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Chronic pelvic pain(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Endometriosis associated Quality of Life(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Quality of life in general(Baseline and week 4, 8, 12 after the 8 hour infusion treatment)
- Productivity costs(12 weeks post-infusion treatment)
- Medical costs(Baseline, 12 weeks post-infusion treatment)
- Pain coping and cognition(Baseline, 12 weeks post-infusion treatment)
- The effect infusion treatment psychedelic effects(On the day of infusion (prior to infusion and during infusion))
- Treatment experience(Directly after infusion)