Recently, the oncology team of Xuzhou Cancer Hospital published a clinical study titled "Observation on the Effect of Calcium Polycarbophil in the Treatment of Opioid-Related Constipation and Its Effect on Serum Inflammatory Factors" in the Chinese core science and technology journal "World Clinical Drugs". This study systematically verified for the first time the efficacy and safety of calcium polycarbophil in the treatment of opioid-related constipation (OIC), providing high-quality evidence-based basis for clinical optimization of intestinal management of patients with constipation. This study is a key publication result of "World Clinical Drugs" in 2025. It not only fills the evidence-based gap in the field of OIC treatment, but also promotes the transformation of constipation treatment from "symptom relief" to "comprehensive management of intestinal health". The dual advantages of efficacy and safety of calcium polycarbophil are expected to become an important basis for updating clinical practice guidelines.

summary

Objective: To observe the clinical effect of calcium polycarbophil in the treatment of opioid-induced constipation (OIC).

Methods: A total of 204 patients with OIC who visited our hospital from June 2022 to December 2023 were selected and divided into a control group and a study group by simple sorting randomization, with 102 cases in each group. They were given rectal enema and oral calcium polycarbophil tablets, respectively, for 2 weeks. The average weekly number of completely spontaneous bowel movements (CSBM), Bristol stool form scale (BSFS), bowel function index (BFI), numerical rating scale (NRS), patient assessment of constipation-quality of life (PAC-QOL) and serum inflammatory factor levels were compared between the two groups before and after treatment.

Results: After treatment, the proportion of patients with an average of CSBM ≥ 3 times per week or an increase of ≥ 1 time compared with the baseline in the study group was higher than that in the control group (50.0% vs. 31.4%, P＜0.05). The proportion of patients with BSFS3-4 in the study group was higher than that in the control group (57.8% vs. 40.2%, P＜0.05). The BFI and PAC-QOL scores, IL-6 and hs-CRP levels in both groups were lower than before (P ＜ 0.05), and those in the study group were lower than those in the control group (P ＜ 0.05). There was no statistical difference in NRS scores between the two groups before and after treatment (P ＞ 0.05).

Conclusion: Calcium polycarbophil can effectively improve constipation symptoms and quality of life in patients with OIC and reduce the levels of serum inflammatory factors, which is worthy of clinical promotion.

Keywords: opioid-related constipation; calcium polycarbophil; cancer pain; constipation; enema

Opioids have been an effective treatment for moderate to severe pain due to their centrally mediated analgesic properties. The World Health Organization considers opioids as the first choice of analgesics for patients with three-stage cancer pain. Opioid-induced constipation (OIC) is the most common adverse reaction in patients taking opioids. According to statistics, the incidence of OIC in patients with chronic non-cancer pain is about 40%, and the incidence of OIC in patients with cancer pain is about 59%. Although μ-opioid receptor antagonists (such as methylnaltrexone and naldemeidine) have been proven to be effective in treating OIC, they are only approved for second-line treatment. Compared with first-line laxatives, they have high cost, narrow indications and serious adverse reactions. Guidelines from many countries recommend laxatives as first-line treatments for OIC. Calcium polycarbophil is a bulk laxative approved for the relief of irritable bowel syndrome and constipation symptoms of various causes. However, the efficacy of calcium polycarbophil on OIC needs to be evaluated. The following report is about its efficacy and safety on OIC.

01. Materials and methods

1.1 General Information

This study was a prospective, single-center, randomized controlled study.The sample size was calculated using PASS11 software, α = 0.05, power = 0.90. According to previous literature and pre-tests, the primary outcome of at least one increase in the average number of completely spontaneous bowel movements (CSBM) per week was professionally considered meaningful, and the proportion of patients in the two groups who increased at least once was approximately 40% and 25%, respectively. According to the 1:1 parallel non-inferiority design, the non-inferiority margin was 0.1, the power was 0.9, and the total number of cases was calculated to be no less than 200, assuming a 10% dropout and non-compliance rate. This study selected 204 patients who developed OIC after receiving opioid analgesics at Xuzhou Cancer Hospital from June 2022 to December 2023.

Inclusion criteria: ① Meet the Rome IV criteria for OIC. ② Aged 18 to 84 years old. ③ Voluntarily participate in this study and sign the informed consent.

Exclusion criteria: ① Patients who received opioid analgesic treatment but the pain was not controlled. ② Intestinal stenosis or intestinal obstruction. ③ Dysphagia. ④ Patients with severe cardiovascular, liver, kidney, hematopoietic system diseases, liver and kidney dysfunction, kidney stones or hypercalcemia.

This study was approved by the Medical Ethics Committee of our hospital (2022XZZL004).

1.2 Grouping

According to the simple sorting random method, 204 patients were divided into the study group and the control group. No restrictive method was used. The patients were numbered according to the order of admission, and the random number table generated by computer was used to divide them into the corresponding groups, with 102 cases in each group. The patients in the control group were given rectal enema (20 ml/tube, 20210804, Zhejiang Suichang Huikang Pharmaceutical Co., Ltd.), 1 tube each time, squeeze the liquid into the anus, and perform it after getting up in the morning. The study group received polycarbophil calcium tablets (0.5 g/tablet, 51422001A, Suzhou Chung-Hwa Chemical&Pharmaceutical Industrial Co., Ltd.), 3 times a day, 2 tablets each time, and both groups were treated for 2 consecutive weeks.

1.3 Efficacy evaluation indicators

Main outcome measure: Average weekly recorded CSBM. CSBM was recorded before treatment and 2 weeks after treatment and counted in weeks.

Secondary outcome indicators: ① Bristol stool form scale (BSFS): record the BSFS for stool characteristics and consistency before and after treatment. ② Numerical rating scale (NRS): record the NRS assessment scores before and after treatment. From 0 to 10 points, 0 points represent no pain, 1 to 3 points for mild pain, 4 to 6 points for moderate pain, and 7 to 10 points for severe pain. The higher the score, the more severe the pain. ③ Bowel function index (BFI): The Chinese version of the BFI scale has 3 questions, namely the degree of straining during defecation, the feeling of incomplete defecation, and the patient's self-satisfaction with defecation. Each question ranges from 0 to 100 points, and the higher the score, the more severe the symptoms. Doctors and patients need to judge the 3 constipation symptoms in the past week. ④ Patient Assessment of Constipation Quality of Life (PAC-QOL): PAC-QOL scores were recorded before and after treatment. ⑤ Serum inflammatory factors: 5 ml of peripheral blood samples were collected on an empty stomach in the morning before and after treatment, and the samples were allowed to stand at room temperature for 30 min, and then centrifuged to obtain the supernatant. Serum inflammatory factors high sensitive C-reactive protein (hs-CRP, Elabscience, A220118) and interleukin (IL)-6 (Shanghai Yiyan Biotechnology Co., Ltd., 220306) were measured by enzyme-linked immunosorbent assay.

1.4 Safety evaluation indicators

Measure the blood routine, urine routine, liver and kidney function of patients before and after treatment. Record adverse events and treatment during the study.

1.5 Statistical analysis

SPSS 26.0 was used for statistical analysis. Count data were expressed as n (%) and the χ 2 test was performed.Measurement data that conformed to normal distribution were expressed as (±s), and group comparisons were performed using the grouped two-sample t test, and paired t test before and after treatment. Measurement data that did not conform to normal distribution were expressed as medians (P25, P75), and Wilcoxon signed rank test was used for unequal variances. Two-sided P < 0.05 was considered statistically significant.

02. Results

2.1 General Information

There was no significant difference in age, gender, disease course and other general data between the two groups (P ＞ 0.05), which showed comparability (see Table 1).

2.2 Comparison of average weekly CSBM

Before treatment, there was no significant difference in the average number of CSBMs per week between the two groups (P ＞ 0.05). After treatment, the average number of CSBMs per week in both groups was higher than that before treatment (P ＜ 0.05), and the number in the study group was higher than that in the control group (P ＜ 0.05), as shown in Table 2.

After two weeks of treatment, 50.0% of the study group had an average of CSBM ≥ 3 times per week or an increase of at least 1 time in CSBM compared with the baseline, which was significantly higher than 31.4% in the control group (P ＜ 0.05), as shown in Table 2.

2.3 BSFS fecal characteristics

Before treatment, there was no significant difference in BSFS stool characteristics between the two groups (P ＞ 0.05). After treatment, the number of patients with BSFS type 1-2 in both groups decreased significantly, and the number of patients with BSFS type 3-4 increased significantly. The BSFS type 3-4 in the study group was higher than that in the control group, and the difference was statistically significant (P ＜ 0.05). See Table 3.

2.4 Comparison of BFI between the two groups

Before treatment, there was no significant difference in the BFI scores between the two groups (P ＞ 0.05). After treatment, the BFI scores of the two groups were lower than those before treatment (P ＜ 0.05), and the scores of the research group were lower (P ＜ 0.05), see Table 4.

2.5 Comparison of NRS between the two groups

Before and after treatment, the NRS scores of the two groups did not change significantly (P ＞ 0.05), see Table 5.

2.6 Comparison of PAC-QOL between the two groups

After treatment, the PAC-QOL scores of both groups decreased significantly (P < 0.05), and the score of the study group was lower than that of the control group (P < 0.05), see Table 6.

2.7 Related serum cytokine indicators

Compared with before treatment, IL-6 in both groups decreased significantly after treatment (P ＜ 0.05), and the level in the research group was lower than that in the control group (P ＜ 0.05). Before and after treatment, the hs-CRP level in the control group did not change significantly (P ＞ 0.05); after treatment, the hs-CRP level in the research group decreased compared with that before treatment (P ＜ 0.05), and the level in the research group was lower than that in the control group (P ＜ 0.05), see Table 7.

2.8 Safety evaluation

During the medication, 1 case (1.0%) of diarrhea occurred in the control group, and it was unclear whether it was related to the medication. In the study group, 3 cases (2.9%) had mild diarrhea, 2 cases (2.0%) had nausea, 2 cases (2.0%) had dry mouth, and 2 cases (2.0%) had abdominal pain, a total of 9 cases of adverse reactions, with an incidence rate of 8.9%. The symptoms gradually improved with the progress of medication, and all adverse reactions disappeared after stopping the medication.

03. Discussion

Constipation is the most common gastrointestinal adverse reaction in patients taking opioids, which puts a burden on patients' physiology, psychology and social communication, and seriously affects their quality of life. The bulk laxative calcium polycarbophil is a highly water-absorbent polymer with unique biological and physical properties. It expands by absorbing 60 to 100 times its own weight of water to promote gastrointestinal motility and relieve defecation difficulties.

The results of this study showed that after treatment, the response rate of CSBM ≥ 3 times or CSBM increased by ≥ 1 times compared with the baseline in the study group was higher than that in the control group. This suggests that calcium polycarbophil tablets are more effective than enema, and this conclusion is supported by relevant literature. After treatment, the BSFS of type 3 to 4 normal stools in the study group was higher than that in the control group, indicating that calcium polycarbophil can restore more OIC patients' hard stools to normal stools. This result has also been confirmed in a multicenter clinical trial of calcium polycarbophil in China. The results of this study showed that the NRS scores of both groups of patients did not change compared with before treatment, indicating that the treatment regimens of both groups did not affect the analgesic effect. The improvement effects of BFI defecation effort, incomplete defecation, and defecation satisfaction in the study group were better than those in the control group, indicating that calcium polycarbophil tablets can significantly promote intestinal peristalsis and relieve constipation symptoms in OIC patients.

The PAC-QOL results showed that the efficacy of the study group after treatment was better than that of the control group. The reasons may include: the laxative effect of calcium polycarbophil tablets is better, and patients are more satisfied with the stool quality; although the adverse reactions of enema are mild, it is less convenient to use; most patients who use opioids for analgesia are elderly, have inconvenient legs or limited activities, poor compliance, and high requirements for medication methods. Therefore, calcium polycarbophil has more advantages in improving the quality of life of patients. Safety results showed that the incidence of adverse reactions in the study group was higher than that in the control group, mainly mild diarrhea, nausea, dry mouth and abdominal pain.

Domestic studies have shown that the incidence of adverse reactions to calcium polycarbophil is 2.28%, mainly including skin allergies and diarrhea.Studies have shown that the incidence of adverse reactions in calcium polycarbophil tablets (11.1%) was not significantly different from that in the control group (7.8%). None of the above clinical trials reported serious adverse reactions, and the symptoms of adverse reactions disappeared after drug withdrawal, with good safety. The pathophysiological mechanism of OIC has not yet been unified. Studies have shown that opioids not only slow down gastrointestinal transit through opioid receptors, but may also damage intestinal permeability and intestinal immune signal transduction, leading to increased inflammation and susceptibility to infection.

The results of this study showed that the IL-6 level in the study group after treatment was lower than that before treatment, suggesting that calcium polycarbophil may be involved in the process of IL-6 reduction. When inflammation occurs in the intestine, the intestinal mucosal barrier is destroyed, the mucosal permeability increases, and pro-inflammatory factors such as IL-6 are released into the blood in large quantities. Calcium polycarbophil may be involved in this anti-inflammatory process. hs-CRP is one of the indicators widely used in clinical practice to assess the level of inflammation in the body. Studies have shown that the level of hs-CRP in patients with irritable bowel syndrome is higher than that in normal people, and the level of hs-CRP in the body is significantly reduced after treatment with calcium polycarbophil, which is consistent with the results of this study. Therefore, the significant improvement in the clinical effect of calcium polycarbophil may be related to the reduction of the levels of pro-inflammatory factors hs-CRP and IL-6. This study also has certain limitations, such as a small sample size and only from a single center, which is prone to sampling errors. In addition, the observation time is short, so the long-term efficacy and safety remain to be evaluated.

04. Conclusion

Calcium polycarbophil can significantly improve the frequency of bowel movements, stool quality and BFI of OIC patients, improve the quality of life, reduce the level of inflammation in the body, and has no effect on the analgesic effect of opioids. It is highly safe and worthy of clinical promotion.

References

Lü Jiao, Zhao Hongying, Zhu Mei. Observation on the effect of calcium polycarbophil in the treatment of opioid-related constipation and its effect on serum inflammatory factors[J]. World Clinical Drugs, 2025, 46(3):243-248.DOI: 10.13683/ j.wph.2025.03.006

Scan the QR code to get the original text