Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial)
Lucía Guilabert, Karina Cárdenas-Jaen, Alicia Vaillo-Rocamora, María Lourdes Ruiz-Rebollo, Federico Bolado, E. Martinez-Moneo, Robin Rivera-Irigoín, Rosa Martín‐Mateos, G. García-Rayado, Antonio López-Serrano, Eva Martí-Marqués, Juan Armando Rodríguez-Oballe, María Francisco-González, Manuel Jiménez‐Moreno, Pablo Cañamares-Orbís, Mar Concepción-Martín, Isabel Pascual-Moreno, A. del Val, Eugenia Lauret-Braña, Claudia Sánchez‐Marin, Andrés J. del Pozo-García, Diego Ledro-Cano, Pedro Zapater, J. Nuñez-Otero, Lorena Bernal-Luján, Vikesh K Singh, Georgios I Papachristou, Pramod K Garg, Bechien Wu, Rajiv Mehta, de-Madaria Enrique
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.