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**:

1. **1L-PEG/AL**: 1 L polyethylene glycol plus ascorbic acid with 0.5 mg linaclotide.

2. **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:

1. **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.

2. **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.

3. **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.