Opioid-induced Constipation in Patients With Cancer Clinical Trial
Official title:
Effect of Electroacupuncture on Opioid-induced Constipation in Patients With Cancer: Study Protocol for a Multicenter Randomized Controlled Trial
| Verified date | July 2022 |
| Source | Guang'anmen Hospital of China Academy of Chinese Medical Sciences |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 100 |
| Est. completion date | December 11, 2021 |
| Est. primary completion date | October 16, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 85 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| China | Guang An Men Hospital | Beijing |
| Lead Sponsor | Collaborator |
|---|---|
| Guang'anmen Hospital of China Academy of Chinese Medical Sciences |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Patients'expectation of the acupuncture efficacy | Participants will be asked to answer the following questions before the intervention: "Do you think acupuncture will be effective in treating the disease in general?" "Do you think acupuncture will be effective in improving the OIC?" and "which acupuncture modalities do you prefer, EA or SA?" For each question, patients will choose one of the following answers: "unclear/whatever", "EA", or "SA" | at baseline | |
| Other | The patient blinding assessment | Five minutes after the end of any treatment in the eighth week the patients will be asked to answer the following question: "Is traditional EA the acupuncture modality that you have received?". | at week 8 | |
| Other | Incidence of adverse events | All adverse events (AEs) t will be recorded throughout the whole trial in case report form. AEs will be categorized as treatment-related (e.g., broken needle, dizziness, fainting, localized hematoma, localized infection or abscess, or some discomforts after acupuncture) and non-treatment-related. Detailed information regarding AEs and serious adverse events (SAEs)-including the name, onset and end date, intensity, relationship with acupuncture and outcome-will be recorded. | week 1 to week 16 | |
| Other | The intensity of cancerous pain evaluation | The mean cancerous pain intensity and worst cancerous pain intensity during the preceding week will be evaluated by 11 grades (from "0=no pain" to "10=worst pain (the strongest pain ever experienced)" at baseline, as well as weeks 2, 4, 6, 8 and 16. | at baseline, at weeks 2, 4, 6, 8 and 16. | |
| Other | The proportion of patients discontinuing the opioid, and those with a =30% weekly mean increase or decrease in the dose of opioid from baseline during weeks 1-8 and weeks 9-16 | The proportion of patients discontinuing the opioid, and those with increase/decrease from baseline of =30% opioid usage per week will be compared between groups during weeks 1-8, and weeks 9-16 | at week 8 and week 16 | |
| Primary | The proportion of responders | A responder 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. | weeks 1-8 | |
| Secondary | Change in the mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16. | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. | weeks 1-8, and weeks 13-16 | |
| Secondary | The proportion of patients with =3 mean weekly spontaneous bowel movements (SBMs) during weeks 1-8 and weeks 13-16 | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. | weeks 1-8, and weeks 13-16 | |
| Secondary | The proportion of patients with an increase of =1 mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16 | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. | weeks 1-8, and weeks 13-16 | |
| Secondary | A Change in the mean weekly complete spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16. | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation. | weeks 1-8, and weeks 13-16 | |
| Secondary | The proportion of patients with =3 mean weekly spontaneous bowel movements (CSBMs) during weeks 1-8 and weeks 13-16 | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation. | weeks 1-8, and weeks 13-16 | |
| Secondary | The proportion of patients with an increase of =1 mean weekly spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16 | An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation. | weeks 1-8, and weeks 13-16 | |
| Secondary | 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 | For stool consistency, each patient was asked to record their stool consistency according to the Bristol Stool Form Scale, on the following seven points scale. (scored from 1 to 7 for stool types 1 to 7, respectively) | weeks 1-8, and weeks 13-16 | |
| Secondary | 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 | For assessment of straining of SBM, each patient was asked to rate his/her score for straining using the following five-point scale: not at all difficulty (0), a little bit difficulty (1), moderately difficulty (2), quite a bit difficulty (3), extremely difficulty (4). | weeks 1-8, and weeks 13-16 | |
| Secondary | A change in the total and subscale score of the Patient Assessment of Constipation-Symptom (PAC-SYM) questionnaire from baseline at weeks 8 and 16 | The PAC-SYM is a 12-item evaluative questionnaire for the chronic constipation, which consists of 4-item abdominal, 3-item rectal, and 5-item stool subscales. Each item score ranges from 0 to 4 in the 2 weeks (14 days) prior to assessment. The, where 0 = symptom absent, 1 = mild,2 = moderate,3 = severe and 4 = very severe. Lower scores indicate a lower symptom burden. Each subscale score will be calculated as the mean of the completed items for that subscale. The total score will be calculated as the mean of all completed items. | week 8 and week 16 | |
| Secondary | A change in the total and subscale scores of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires from the baseline at weeks 8 and 16 | The PAC-QOL is a 28-item self-reported instrument for assessing the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. It is divided into four subscales: physical discomfort (items 1-4), psychosocial discomfort (items 5-12), worries/concerns (items 13-23), and satisfaction (items 24 to 28). Each of the item scores ranges from 0 (not at all) to 4 (extremely), with lower scores indicating a better quality of life. For each visit, individual subscale scores will be calculated as the mean of the completed items for that subscale. | week 8 and week 16 | |
| Secondary | Patients' global assessment of treatment efficacy | each patient was asked to rate his/her efficacy of treatment using the following 7-point self-reporting scale: markedly worse (1), moderately worse (2),slightly worse (3), no change (4), slightly improved (5), moderately improved (6), markedly improved (7). | week 8 and week 16 | |
| Secondary | The proportion of patients using rescue medicine and the mean frequency of rescue medicine use per week during weeks 1-8 and weeks 9-16 | The proportion of patients using rescue medicine will be compared between groups during weeks 1-8, and weeks 9-16. The mean frequency of using rescue medicine per week during weeks 1-8 equals the total of rescue medicine consumption divided by 8. The mean frequency of using rescue medicine per week during weeks 9-16 equals the total of rescue medicine consumption divided by 8. | weeks 1-8, and weeks 9-16 |