Application of oral sulfate solution combined with linaclotide in bowel preparation for colonoscopy

Objective High-quality bowel preparation is essential for accurate colonoscopy. Currently, linaclotide is used as an adjunctive agent supporting bowel preparation, but evidence for its combination with oral sulfate solution (OSS) remains limited. This study aimed to evaluate whether the addition of linaclotide to OSS could improve the efficacy of bowel preparation. Methods This single-blind, randomized controlled trial enrolled outpatients scheduled for colonoscopy. Participants were randomly assigned (1:1:1) to one of three groups: the OSS + Linaclotide group, the OSS group, or the polyethylene glycol (PEG) group. The primary outcome was the adequate bowel preparation rate, while secondary outcomes included tolerability, colonoscopy findings, and safety. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) population, and safety was evaluated in the as-treated population. Results A total of 370 patients were included in the mITT analysis. There was no statistically significant difference in the adequate bowel preparation rate between the OSS + Linaclotide group and the OSS group (86.5% vs. 88.0%; unadjusted relative risk [RR], 0.98; 95% confidence interval [CI], 0.89–1.08; p = 0.723). In the unadjusted analysis, both the OSS + Linaclotide group (86.5% vs. 73.9%; unadjusted RR, 1.17; 95% CI, 1.03–1.33; p = 0.013) and the OSS group (88.0% vs. 73.9%; unadjusted RR, 1.19; 95% CI, 1.05–1.35; p = 0.005) demonstrated significantly higher adequate bowel preparation rates than the PEG group. Moreover, the analysis adjusted for covariates showed no statistically significant differences between groups ( p > 0.05). In exploratory analysis, patient-reported incidence of bloating was less frequent in the OSS + Linaclotide group (4.0% vs. 16.0% vs. 11.8%, p = 0.007), with no increase in nausea, vomiting, or other adverse events. No significant between-group differences were observed in other tolerability measures or colonoscopy findings. Conclusion This study did not meet its primary endpoint. Linaclotide added to OSS provided no additional cleansing efficacy over OSS alone or PEG. Exploratory analysis found that the combination may reduce bloating, a potential tolerability advantage requiring further verification in future studies.