Simvastatin in the Prevention of Recurrent Pancreatitis: Design and Rationale of a Multicenter Triple-Blind Randomized Controlled Trial, the SIMBA Trial

Abstract

Background: One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP. Methods: The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events. Discussion: The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT04021498.

Keywords: acute pancreatitis; chronic pancreatitis; hydroxymethylglutaryl-CoA reductase inhibitors; idiopathic; prevention; recurrent; simvastatin; statins.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Cárdenas-Jaén, Vaillo-Rocamora, Gracia, Garg, Zapater, Papachristou, Singh, Wu and de-Madaria.

Figures

Figure 1

Flowchart for SIMBA trial according to CONSORT 2010 and SPIRIT 2013 recommendations. (A) ≥18 years old, at least 2 episodes of AP or acute flares of chronic pancreatitis, written informed consent. (B) <2 episodes of pancreatitis or acute flares of chronic pancreatitis in the last 12 months; stain consumption in the previous year; contraindications to the use of statins; cholelithiasis or choledocholithiasis diagnosed in the last episode of pancreatitis; endoscopic sphincterotomy and/or cholecystectomy and/or pancreatic surgery between last episode of AP and recruitment or patients who are expected to undergo one of this techniques in less than a year; serum triglycerides >500 mg/dL without previous specific treatment before the last episode of pancreatitis, or in patients expected to have a change in their specific hypertriglyceridemia treatment in <1 year; primary hyperparathyroidism that has been operated between last episode of pancreatitis and recruitment or will be operated in <1 year; iatrogenic pancreatitis; abstinence syndrome due to alcohol or drugs and/or delirium tremens in the last 6 months before recruitment; previous (last year) failure to attend follow-up medical visits, social problems that may be associated to failure to take the medication or to perform an adequate follow-up; pregnancy or breastfeeding. (C) Intention-to-treat (primary analysis) and per-protocol analysis. Tx, treatment.