Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial)

Clinical Snapshot

Key Findings

• P Value: p=0.88 (not significant)

• Effect Size: OR 1.07 (no benefit demonstrated)

• Primary Outcome: Pancreatitis recurrence: 46.2% simvastatin vs 44.4% placebo

• Nnt Or Sensitivity: NNT not calculable (no benefit demonstrated); NNH for diabetes: 11 patients

• Confidence Interval: 95% CI 0.43 to 2.66

Clinical Application

Simvastatin readily available and affordable, but evidence does not support use for pancreatitis prevention Simvastatin available on PBS for cardiovascular indications. TGA approval would not extend to pancreatitis prevention based on this evidence. RACGP guidelines would not recommend off-label use without proven benefit Australian patients with recurrent acute pancreatitis or chronic pancreatitis flares meeting study criteria

Abstract

BACKGROUND: Recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP) have limited preventive options beyond addressing the underlying aetiology. Statins, due to their anti-inflammatory properties, have been proposed as a potential prophylactic treatment. OBJECTIVE: We aimed to evaluate whether simvastatin could reduce the recurrence of pancreatitis. DESIGN: At 23 centres, we conducted a triple-blind, randomised, controlled, superiority trial enrolling patients with at least two episodes of RAP or CP flares in the previous 12 months. Participants were randomly assigned to receive simvastatin or placebo for 1 year. The primary endpoint was the recurrence of pancreatitis. The target sample size was 144 patients; however, an interim analysis was planned in the event of slow recruitment. RESULTS: A total of 85 patients (42.1% women) were included in the interim analysis. In the intention-to-treat analysis, no significant differences were observed regarding recurrence: 46.2% simvastatin versus 44.4% placebo; OR 1.07, 95% CI 0.43 to 2.66; p=0.88, or time to recurrence. No statistically significant differences were observed in recurrence in per-protocol analysis (35.5% simvastatin vs 41.9% placebo; OR 0.76, 95% CI 0.27 to 2.12; p=0.60). Development of diabetes mellitus was more frequent in the simvastatin group (4 vs 0 patients; OR not calculable, p=0.04). CONCLUSION: This trial, evaluating simvastatin versus placebo for the prevention of pancreatitis, did not demonstrate a reduction in recurrence rate, although results might be underpowered due to early termination. The relationship between statins in these patients and new-onset diabetes requires further investigation. TRIAL REGISTRATION NUMBER: NCT04021498.

References

1. 1.Guilabert, L., Cárdenas-Jaén, K., Vaillo-Rocamora, A., Ruiz-Rebollo, M. L., Bolado-Concejo, F., Martínez-Moneo, E., Rivera-Irigoin, R., Martin-Mateos, R., García-Rayado, G., López-Serrano, A., Martí-Marqués, E., Rodríguez-Oballe, J. A., Francisco-González, M., Jiménez-Moreno, M. A., Cañamares-Orbís, P., Concepción-Martín, M., Pascual-Moreno, I., Del Val, A., Lauret-Braña, E., ... de-Madaria, E. (2026). Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial). Gut. https://doi.org/10.1136/gutjnl-2025-337154