Efficacy of 1 L polyethylene glycol plus ascorbic acid with linaclotide versus senna for bowel preparation: A multicenter, endoscopist-blinded, randomized controlled trial (Apple trial).

Abstract

Objectives: No bowel preparation for colonoscopy achieves optimal efficacy and tolerability. Combining polyethylene glycol plus ascorbic acid (PEG-Asc) with adjuvants has been explored to enhance cleansing efficacy and reduce the required volume. This study aimed to evaluate whether adding 0.5 mg linaclotide to 1-L PEG-Asc (1 L-PEG/AL) improves superior cleansing compared to adding 24 mg senna (1 L-PEG/AS), which we previously reported to be non-inferior to the standard regimen of 2 L PEG-Asc.

Methods: A multicenter, endoscopist-blinded, randomized controlled trial was conducted at five centers in Japan with outpatients scheduled for colonoscopy. The primary outcome was adequate bowel preparation (BP), evaluated using the Boston Bowel Preparation Scale. Analyses were stratified based on low- and high-risk groups for inadequate BP.

Results: Between April 2022 and April 2023, 1,464 patients were randomized to the 1L-PEG/AL (n=733) or 1L-PEG/AS (n=731). The 1L-PEG/AL demonstrated higher adequate BP rates (92% vs. 86%, P=0.001) compared to 1L-PEG/AS. Both groups experienced similar adverse events and expressed high willingness for repeat BP (83% vs. 81%, P=0.49). In high-risk patients (n=892), 1L-PEG/AL had significantly higher adequate BP rates (94% vs. 86%, P<0.001), whereas rates were comparably high in low-risk patients (n=539) (94% vs. 94%, P=0.66).

Conclusions: The linaclotide regimen was superior to the senna regimen in terms of BP efficacy without reducing tolerability. It can be a promising new option for BP, especially in patients at a high-risk of inadequate BP.