Efficacy Of Different Regimens Of Linaclotide Combined With Polyethylene Glycol Electrolytes Powder In Pre-Colonoscopy Bowel Preparation:A Randomized,Controlled,Single-Blind,Single-Center And Non-Inferiority Trial

Background Colonoscopy is the standard procedure for assessing colon disease and screening for colorectal cancer and bowel cleansing prior to colonoscopy is key.Polyethylene glycol electrolytes powder(PEG)solution is the preferred bowel preparation agent recommended by the European Society of Gastrointestinal Endoscopy(ESGE)Guideline,but drinking a large volume of it over a short period of time is associated with poor tolerability among patients.Linaclotide(L),primarily utilized to treat irritable bowel syndrome with constipation(IBS-C),is to be able to improve bowel cleansing quality,but the specific dosing regimen still requires further confirmation.Aim Exploring the effectiveness and tolerability of different dosing regimens of PEG + L for intestinal preparation.Methods This study was a randomized,controlled,single-blind and non-inferiority trial that randomly stratified the 324 included patients into 3 groups: 2L PEG +split-dose L(Group A),2L PEG + single-dose L(Group B),and 3L PEG(Group C).The primary outcome indicators were the success rate of bowel preparation and high-quality bowel cleansing rate assessed based on the Boston Bowel Preparation Scale(BBPS).The secondary endpoints were patient tolerability,safety,defecating frequency,the first time of defecation,achieving a preferable defecation time,and adenoma and polyp detection rates,sleeping quality,cecal intubation rate.Results The cleansing efficacy analysis was conducted on the 324 included patients(Group A,n = 108;Group B,n = 105;Group C,n = 111).Non-inferiority was demonstrated between 2L PEG + L and 3L PEG in terms of the successful rate of bowel preparation(95.4% vs.91%,P = 0.2;84.8% vs.91%,P = 0.160).Group A had significantly higher overall BBPS score than Groups C(8.3±1.3 vs.7.7±1.6,P = 0.011)and B(8.3±1.3 vs.7.6±1.6,P = 0.001).Besides,Group A also exhibited visibly increased high-quality bowel cleansing rate than Groups C(68.5% vs.45%,P < 0.001)and B(68.5% vs.44.8%,P < 0.001).Further evaluation revealed that Group A had visibly increased high-quality cleansing rate of the right colon than Groups C(77.8% vs.48.6%,P < 0.001)and B(77.8% vs.45.7%,P < 0.001).It was also discovered that 2L PEG + L was obviously better tolerated(in terms of overall satisfaction,willingness to take again;all P values < 0.01)and safer(15.7% vs.28.8%,P = 0.02;16.2% vs.28.8%,P = 0.027)among patients compared with 3L PEG.Conclusion 2L PEG + L displayed non-inferior bowel cleansing efficacy as well as better tolerability and safety,as compared with 3L PEG.Furthermore,2L PEG +split-dose L could lead to significantly superior bowel cleansing quality,as compared with 2L PEG + single-dose L and 3L PEG.