Background and Aims: Some adjuvants have been added to improve the quality of bowel preparation (BP) for colonoscopy and to reduce the total amount of BP solution required. However, the appropriate type of adjuvant remains unknown. Linaclotide is a guanylate cyclase-C receptor agonist and is currently approved for the treatment of chronic constipation. We hypothesized that the addition of linaclotide to low volume of polyethylene glycol plus ascorbic acid (PEG-Asc) would yield better cleansing compared to the addition of senna, for which we recently reported the non-inferiority to the standard BP (Maeda et al. Digestive Endoscopy 2023).
Methods: We did a multicenter, endoscopist-blinded, randomized controlled trial at five centers in Japan. Outpatients scheduled for colonoscopy were randomized (1:1) to 1-L PEG-Asc plus 0.5 mg linaclotide (1L-PEG/AL) or 1-L PEG-Asc plus 24 mg senna (1L-PEG/AS) group. Boston Bowel Preparation Scale (BBPS) was used to evaluate the quality of BP, and adequate BP was defined as a total score ≥6 and each segmental score ≥2. Adverse events and tolerability were surveyed using questionnaires. Tolerability was evaluated by willingness to repeat the BP. We also performed the stratified analysis between low- and high-risk groups for inadequate BP. Patients were considered at high risk for inadequate BP if they met at least one of the following factors: >75 years old, BMI >25, chronic constipation, diabetes mellitus, stroke, Parkinson’s disease, or use of tricyclic antidepressants.
Results: Between April 2022 and April 2023, 1464 patients were randomly assigned 1L-PEG/AL (n=733) or 1L-PEG/AS (n=731) group. After randomization, 11 patients in the 1L-PEG/AL group and 22 in the 1L-PEG/AS group withdrew from the study. Finally, 720 patients in the 1L-PEG/AL group and 711 patients in the 1L-PEG/AS group were included in the per protocol (PP) analysis. The baseline characteristics of both groups were comparable. In the intention to treat (ITT) and PP analysis, 1L-PEG/AL group showed higher adequate BP rates compared with the 1L-PEG/AS group (92% vs. 86%, 94 % vs 89 %, respectively P<0.01); the overall BBPS was 7.6±1.5 and 7.4±1.6, respectively (P<0.01). Adverse events including nausea, vomiting, abdominal pain and sleep disturbance, and willingness to repeat the BP were comparable between the two groups. In risk-stratified analysis, the rate of adequate BP was significantly higher in the 1L-PEG/AL group in high-risk patients (n=824) (94% vs. 85%, P<0.01), whereas comparable high rates of adequate BP rates were found between two regimens in low-risk patients (n=607) (93% vs. 94%, P=0.74).
Conclusions: The linaclotide regimen was superior to the senna regimen in terms of BP efficacy without reducing tolerability. It can be a new promising option for BP, especially in patients at high risk of inadequate BP.

Table 1: Outcomes of bowel preparation

Table 2: Adverse events and tolerability

Masami Nakatani

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