Efficacy of PEG–Ascorbic Acid Plus Linaclotide vs Senna for Bowel Preparation (APPLE Trial)
The APPLE trial (Efficacy of PEG–Ascorbic Acid Plus Linaclotide vs Senna for Bowel Preparation) was a multicenter, endoscopist-blinded, randomized controlled trial conducted across five centers in Japan. The study aimed to evaluate whether adding linaclotide to a low-volume bowel preparation regimen (polyethylene glycol plus ascorbic acid, 1L-PEG) improves bowel cleansing efficacy compared to senna.
Study Design:
- Participants: A total of 1,464 outpatients scheduled for colonoscopy.
- Intervention Groups:
1L-PEG/AL: 1 L polyethylene glycol plus ascorbic acid with 0.5 mg linaclotide.
1L-PEG/AS: The same regimen with 24 mg senna.
- Primary Endpoint: Adequate bowel preparation assessed using the Boston Bowel Preparation Scale (BBPS).
Key Findings:
- Efficacy:
- The linaclotide regimen (1L-PEG/AL) achieved significantly higher rates of adequate bowel preparation compared to the senna regimen (1L-PEG/AS): 92% vs 86%.
- Linaclotide showed superior overall and segmental BBPS scores.
- The benefit of linaclotide was most pronounced in high-risk patients for inadequate bowel preparation, where adequacy reached 94% with linaclotide compared to 86% with senna.
- In low-risk patients, both regimens performed equally well.
- Tolerability and Safety:
- Both regimens had similar tolerability, with comparable rates of side effects such as nausea, abdominal pain, sleep disturbances, and willingness to repeat the preparation.
- Linaclotide led to an earlier onset of bowel movements and increased defecation before the intake of PEG, without increasing adverse events.
- Colonoscopy Outcomes:
- Colonoscopy completion rates, procedure times, and lesion detection rates were comparable between the two regimens.
Conclusion:
The APPLE trial demonstrated that the linaclotide-enhanced low-volume bowel preparation regimen (1L-PEG/AL) provides superior cleansing efficacy compared to the senna regimen (1L-PEG/AS), particularly in high-risk patients, while maintaining similar safety and patient acceptability. Linaclotide represents a promising option for improving bowel preparation, especially in patients at high risk of inadequate cleansing.
