SIMBA Trial - GUT Jan 2026

The SIMBA Trial, as described in the provided context, was a triple-blind, randomised, controlled, superiority trial aimed at evaluating whether simvastatin could reduce the recurrence of pancreatitis in patients with recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP). The trial was conducted across 23 centres and included patients who had experienced at least two episodes of RAP or CP flares in the previous 12 months.

### Key Details and Findings from the SIMBA Trial:

1. **Objective**:

The primary goal was to test the efficacy of simvastatin, a statin with anti-inflammatory properties, as a prophylactic treatment to prevent the recurrence of pancreatitis.

2. **Design**:

• **Randomisation**: Patients were randomly assigned to receive either simvastatin or a placebo for 1 year.
• **Blinding**: The trial was triple-blind, ensuring that patients, investigators, and statisticians were unaware of the treatment allocation.
• **Primary Endpoint**: The recurrence of pancreatitis was the primary measure of the trial's success.

3. **Participants**:

The target sample size was 144 patients, but due to slow recruitment, an interim analysis was conducted with 85 patients (42.1% women).

4. **Results**:

• **Recurrence Rate**:
• In the intention-to-treat analysis, no statistically significant difference was observed between the simvastatin group (46.2% recurrence) and the placebo group (44.4% recurrence). The odds ratio (OR) was 1.07 (95% CI 0.43 to 2.66; p=0.88).
• In the per-protocol analysis, recurrence rates were 35.5% for simvastatin and 41.9% for placebo (OR 0.76, 95% CI 0.27 to 2.12; p=0.60).
• **Time to Recurrence**: No significant differences were observed between the groups.
• **Adverse Events**: Development of diabetes mellitus was more frequent in the simvastatin group (4 patients vs 0 patients in the placebo group; p=0.04).

5. **Conclusion**:

• The trial did not demonstrate that simvastatin reduces the recurrence rate of pancreatitis.
• The results may be underpowered due to the early termination of the study.
• The observed association between statins (simvastatin) and new-onset diabetes mellitus warrants further investigation.

6. **Implications**:

• While statins have anti-inflammatory properties, their role in preventing pancreatitis recurrence remains uncertain based on this trial.
• The potential risk of new-onset diabetes mellitus in patients taking statins, particularly simvastatin, should be explored further in future studies.

### Note:

The trial's results highlight the importance of adequately powered studies to draw definitive conclusions. Any further references to the SIMBA trial in publications, such as GUT in January 2026, may include additional analyses, follow-up studies, or insights based on the trial's findings.