Effect of Electroacupuncture on Opioid-induced Constipation in Patients With Cancer: Study Protocol for a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Number of Participants With Response
研究概览
简要总结
Approximately 70-80% of patients with advanced disease will be affected by moderate to severe pain. Opioid analgesics represented by morphine and oxycodone are the cornerstone of cancer-pain management, and recommended for use in the management of moderate to severe cancer pain according to WHO Cancer Pain Relief Guidelines. One view is that a trial of systemic opioid therapy should be administered to all cancer patients with pain of moderate or greater severity regardless of the pain mechanism. Although opioids analgesics do work well as relieving pain and improving quality of life via their action at opioid receptors in the central nervous system (CNS) and the peripheral nervous system, they also have powerful adverse effects. The overall occurrence of opioid-related adverse drug events has ranged from1.8% to 13.6%. Opioid-induced constipation (OIC), one of the most prevalent adverse events (AEs) in patients receiving opioid analgesics, defined as a change in baseline bowel habits or defecatory patterns following initiation, alteration, or increase in opioid therapy. The prevalence of OIC has been estimated to affect 41% of patients with chronic noncancer pain taking opioids and 94% of cancer patients taking opioids for pain. Unlike many other opioid-related AEs, OIC is persistent and rarely tolerated. OIC impacts pain control, patients' quality of life and may cause patients to reduce the dose or discontinue opioid use.
Acupuncture, a traditional Chinese medicine, has been used to treat gastrointestinal disease including constipation for thousands of years. Two systematic reviews concluded that acupuncture can improve spontaneous bowel movements for functional constipation, and our recent study indicated that electroacupuncture(EA) could increase complete spontaneous bowel movements and is safe for chronic severe functional constipation. Acupuncture could improve gastrointestinal function via facilitating gastrointestinal motility. Currently, there is little detailed information available regarding the acupuncture use for OIC. The objective of this study is to assess the efficacy and safety of EA for OIC in patients with cancer.
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 (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cancer patients who conformed to all the following conditions will be further screened for eligibility:
- •Cancer patients must meet the Rome IV[1] diagnostic criteria for OIC: New or worsening symptoms of constipation following initiation, alteration, or increase in opioid treatment. For patients with a history of chronic functional constipation, he/she must have worsening symptoms of constipation when the opioid therapy is initiated, changed, or the dose is increased;
- •Patients recruited in this trial must have a history of OIC symptoms for at least 1 week;
- •Patients must be ≥18 years of age and ≤85 years of age;
- •Patient's cancer condition must be stable with a life expectancy that is more than six months;
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
- •Patients must have been receiving a relatively stable maintained opioid regimen, consisting of a total daily dose of 30 mg to 1000 mg oral morphine equivalents for at least 2 weeks prior to screening for cancer pain. Furthermore, it must be anticipated that the opioid will be maintained for at least 10 weeks;
- •The SBM frequency of the patients must be ≤ 2 times a week when laxatives are not being taken;
- •Patients must be capable of oral intake of drugs, food and beverages;
- •Provision of written informed consent before participation.
排除标准
- •Participants who fulfill any of the following criteria will be excluded:
- •Patients diagnosed with clinically significant abnormal defecation due to structural abnormalities of the gastrointestinal tract and other tissues related to gastrointestinal tract (not including OIC): inflammatory bowel disease, rectal prolapse, gastrointestinal obstruction, peritoneal metastasis, or peritoneal tumor at the time of enrollment;
- •Patients with a history of gastrointestinal tract operation, abdominal operation, or abdominal adhesion within one month prior to screening; history of intestinal obstruction within three months prior to screening;
- •Diagnosis of active diverticular disease; or severe hemorrhoid; or anal fissure; or artificial rectum or anus;
- •Patients with an intraperitoneal catheter or a feeding tube;
- •Diagnosis of pelvic disorder which are considered to have obvious effects on the intestinal transport of feces (such as uterine prolapse ≥degree 2, uterine fibroids [located in the posterior of the uterus with a diameter ≥ 5 cm] affecting bowel movement);
- •Patients that are being treated with a new cancer chemotherapy, which had never been administered in the past, within 14 days of the screening or are scheduled to receive such therapy during the study;
- •Patients that received radiotherapy within 28 days of the screening or are scheduled to receive such therapy during the study;
- •Patients that underwent a surgery or intervention that is considered to have an obvious effect on the gastrointestinal functions within 28 days of the screening or are scheduled to receive surgery or intervention which is considered to have obvious effects on the gastrointestinal functions during the study, or scheduled to receive surgery or intervention which will be anticipated to prevent the patients from completing the trial;
- •Patients with uncontrolled hyperthyroidism, severe hypertension, heart disease, systematic infection or blood coagulation disorders (hypercoagulation status or hemorrhagic tendency) at the time of study inclusion;
- •Patients that consumed >4 additional opioid doses per day, for breakthrough pain, for more than 3 days during the baseline period, or if their maintenance opioid dosing regimen was modified during this period;
- •Patients with severe cancerous pain (e.g., typical average daily pain intensity rating of 7 to 10 on a numerical rating scales (NRS; 0 [no pain] to 10 [the worst pain possible]) after the use of routine dose and frequency of opioids) refractory to opioid therapy;
- •Patients with a history of opioid discontinuation due to severe adverse events or patients that are expected to discontinue opioid use due to the potential risk of adverse events;
- •Patients that received an opioid receptor antagonist within one month of the screening, or those who are scheduled to receive such therapy during the study;
- •Patients with a history of nerve neurolysis;
- •Patients with severe cognitive impairment, aphasia, or psychiatric disorders; abdominal aortic aneurysm; hepatomegaly(liver span > 14cm at the mid-clavicular line by ultrasound examination); or splenomegaly (spleen length [cranial to caudal] > 13cm by ultrasound examination);
- •Patients that have received acupuncture within three months of the screening;
- •Other patients who are considered ineligible for the study by the investigator on the basis of concomitant therapy and medical findings.
结局指标
主要结局
Number of Participants With Response
时间窗: weeks 1-8
A responder（Participant With Response） is defined as a patient that has at least three spontaneous bowel movements (SBMs) per week and an increase of at least one SBM a week from the baseline for at least 6 of the 8 weeks of the treatment period.
次要结局
- A Change in the Mean Weekly Spontaneous Bowel Movements (SBMs) From the Baseline During Weeks 1-8 and Weeks 13-16.(weeks 1-8, and weeks 13-16)
- Number of Participants With ≥3 Mean Weekly Spontaneous Bowel Movements (SBMs) During Weeks 1-8(weeks 1-8)
- Number of Participants With ≥3 Mean Weekly Spontaneous Bowel Movements (SBMs) During Weeks 13-16(weeks 13-16)
- Number of Participants With an Increase of ≥1 Mean Weekly Spontaneous Bowel Movements (SBMs) From the Baseline During Weeks 1-8(weeks 1-8)
- Number of Participants With an Increase of ≥1 Mean Weekly Spontaneous Bowel Movements (SBMs) From the Baseline During Weeks 13-16(weeks 13-16)
- A Change in the Mean Weekly Complete Spontaneous Bowel Movements (CSBMs) From the Baseline During Weeks 1-8 and Weeks 13-16.(weeks 1-8, and weeks 13-16)
- Number of Participants With ≥3 Mean Weekly Spontaneous Bowel Movements (CSBMs) During Weeks 1-8(weeks 1-8)
- Number of Participants With ≥3 Mean Weekly Spontaneous Bowel Movements (CSBMs) During Weeks 13-16(weeks 13-16)
- Number of Participants With an Increase of ≥1 Mean Weekly Spontaneous Bowel Movements (CSBMs) From the Baseline During Weeks 1-8(weeks 1-8)
- Number of Participants With an Increase of ≥1 Mean Weekly Spontaneous Bowel Movements (CSBMs) From the Baseline During Weeks 13-16(weeks 13-16)
- A Change in the Mean Bristol Stool Form Scale Score for Stool Consistency of Spontaneous Bowel Movements (SBMs) From the Baseline During Weeks 1-8 and Weeks 13-16(weeks 1-8, and weeks 13-16)
- A Change in the Mean Score for the Straining of Spontaneous Bowel Movements (SBMs) From the Baseline During Weeks 1-8 and Weeks 13-16(weeks 1-8, and weeks 13-16)
- A Change in the Total Score of the Patient Assessment of Constipation-Symptom (PAC-SYM) Questionnaire From Baseline at Weeks 8 and 16(week 8 and week 16)
- A Change in the Total Scores of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaires From the Baseline at Weeks 8 and 16(week 8 and week 16)
- Patients'Global Assessment of Treatment Efficacy(week 8 and week 16)
- Number of Participants Using Rescue Medicine During Weeks 1-8 and Weeks 9-16(weeks 1-8, and weeks 9-16)
- The Mean Frequency of Rescue Medicine Use Per Week During Weeks 1-8 and Weeks 9-16(weeks 1-8, and weeks 9-16)
研究者
Liu Zhishun
Principal Investigator
Guang'anmen Hospital of China Academy of Chinese Medical Sciences