A Prospective, Multicenter, Randomized, Parallel-controlled, Superiority Trial

A Randomized Controlled Clinical Study of Shouhui Tongbian Capsule in the Treatment of Opioid-Induced Constipation

This study intends to design and conduct a prospective, multicenter, randomized, parallel-controlled, superiority trial to evaluate the symptom-relieving effects of Shouhui Tongbian Capsule on opioid-induced constipation (OIC) in cancer patients, including defecation frequency, stool consistency, symptom scores, quality of life and other indicators, and to systematically observe its safety in clinical application. Through analysis of intestinal flora, the mechanism of Shouhui Tongbian Capsule in regulating intestinal function will be revealed. By screening the optimal population for Shouhui Tongbian Capsule in the treatment of OIC, evidence will be provided for optimizing individualized medication.

The primary efficacy endpoint is the proportion of responders at week 2 of treatment, defined as an increase of ≥1 in the average weekly number of spontaneous bowel movements (SBMs) compared with baseline and at least one SBM during that week. Secondary endpoints include weekly number of SBMs, weekly number of complete spontaneous bowel movements (CSBMs), Bristol Stool Form Scale score, straining score, Patient Assessment of Constipation-Symptoms (PAC-SYM) score, and Patient Assessment of Constipation-Quality of Life (PAC-QOL) score.

Safety endpoints mainly include the incidence of adverse events and changes in vital signs, electrocardiography, routine blood and urine tests, as well as liver and renal function before and after treatment. Meanwhile, based on clinical study data, the characteristics of the optimal population for Shouhui Tongbian Capsule in treating OIC will be identified to further enrich the application scenarios of this capsule for OIC.

Inclusion Criteria:

1. Must meet the diagnostic criteria for **opioid-induced constipation (OIC) according to the Rome IV Criteria**.
2. Patients enrolled in the trial must have a history of OIC symptoms for at least 1 week.
3. Patients must be aged ≥ 18 years and ≤ 85 years.
4. Patients must have stable cancer status with a life expectancy of more than 6 months.
5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
6. Patients must be on a relatively stable maintenance regimen of opioids, including a daily morphine-equivalent dose of 30 mg to 1000 mg for at least 2 weeks prior to the screening period. In addition, opioid therapy is expected to continue for at least 10 weeks.
7. Patients must have a spontaneous bowel movement (SBM) frequency of ≤ 2 times per week without laxative use.
8. Patients must be able to take medications, food, and fluids orally.
9. Voluntarily participate in the trial and have signed the informed consent form.
10. No use of any prokinetic agents for at least 1 week prior to randomization.

Exclusion Criteria:

1. Patients diagnosed with clinically significant defecation disorders at enrollment caused by structural abnormalities of the gastrointestinal tract and other gastrointestinal-related tissues (excluding OIC): inflammatory bowel disease, rectal prolapse, gastrointestinal obstruction, peritoneal metastasis or peritoneal tumors.
2. Patients with a history of gastrointestinal surgery, abdominal surgery or abdominal adhesions within 1 month before screening; or a history of intestinal obstruction within 3 months before screening.
3. Diagnosis of active diverticular disease; or severe hemorrhoids; or anal fissure; or artificial rectum or anus.
4. Patients with intra-abdominal catheters or feeding tubes.
5. Diagnosis of pelvic diseases considered to significantly affect intestinal transit of feces (e.g., uterine prolapse ≥ grade 2, uterine fibroids [located posteriorly with diameter ≥ 5 cm] affecting defecation).
6. Patients who received a new chemotherapy regimen never used before within 14 days after screening, or who planned to receive such treatment during the study period.
7. Patients who received radiotherapy within 28 days after screening or planned to receive such treatment during the study period.
8. Patients who underwent surgery or intervention considered to significantly affect gastrointestinal function within 28 days after screening, or planned to undergo such surgery or intervention during the study period, or planned to undergo surgery or intervention expected to prevent completion of the trial.
9. Patients with uncontrolled hyperthyroidism, severe hypertension, heart disease, systemic infection or coagulation disorders (hypercoagulable state or bleeding tendency) at study enrollment.
10. Patients who took >4 additional opioid doses per day for breakthrough pain for more than 3 days during the baseline period, or who modified the maintenance opioid dosing regimen during this period.
11. Patients with severe cancer pain unresponsive to opioid therapy at regular doses and frequencies (e.g., typical mean daily pain intensity rating of 7 to 10 on the Numerical Rating Scale (NRS; 0 [no pain] to 10 [worst possible pain])).
12. Patients with a history of opioid discontinuation due to serious adverse events, or for whom opioid discontinuation is anticipated due to potential risk of adverse events.
13. Patients treated with opioid receptor antagonists within 1 month before screening.
14. Unconsciousness, psychosis, or inability to express subjective symptoms.
15. Patients who have participated in or are participating in other clinical trials within the past 3 months.
16. Other patients considered ineligible for the study by the investigator based on concomitant treatments and medical findings.