Effect of Electroacupuncture on Opioid-induced Constipation in Patients With Cancer

Inclusion Criteria:

Cancer patients who conformed to all the following conditions will be further screened for eligibility:

1. 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;
2. Patients recruited in this trial must have a history of OIC symptoms for at least 1 week;
3. Patients must be ≥18 years of age and ≤85 years of age;
4. Patient's cancer condition must be stable with a life expectancy that is more than six months;
5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
6. 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;
7. The SBM frequency of the patients must be ≤ 2 times a week when laxatives are not being taken;
8. Patients must be capable of oral intake of drugs, food and beverages;
9. Provision of written informed consent before participation.

Exclusion Criteria:

Participants who fulfill any of the following criteria will be excluded:

1. 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;
2. 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;
3. Diagnosis of active diverticular disease; or severe hemorrhoid; or anal fissure; or artificial rectum or anus;
4. Patients with an intraperitoneal catheter or a feeding tube;
5. 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);
6. 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;
7. Patients that received radiotherapy within 28 days of the screening or are scheduled to receive such therapy during the study;
8. 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;
9. 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;
10. 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;
11. 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;
12. 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;
13. 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;
14. Patients with a history of nerve neurolysis;
15. 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);
16. Patients that have received acupuncture within three months of the screening;
17. Other patients who are considered ineligible for the study by the investigator on the basis of concomitant therapy and medical findings.