Evaluation of Simvastatin for the Prevention of Recurrent Pancreatitis: A Triple-Blind, Randomized Controlled Trial

The primary objective of this study is to evaluate the efficacy of **simvastatin** in reducing the incidence of new episodes of acute pancreatitis (AP) in patients with recurrent pancreatitis (RP) compared to a placebo. This is clinically relevant as recurrent pancreatitis can lead to significant morbidity, and finding an effective preventive treatment could improve patient outcomes and reduce healthcare burdens.

Secondary objectives include comparing the prevalence of imaging signs of chronic pancreatitis, such as calcifications and/or a dilated ductal system, as well as assessing endocrine and exocrine pancreatic function at the end of the follow-up period. Additionally, the study aims to provide data for a potential larger-scale project if a non-significant trend towards the effectiveness of simvastatin is observed.

The clinical trial focuses on **recurrent pancreatitis** and involves a study population comprising both male and female adults aged 18 years and older. Participants are required to have experienced at least two episodes of acute pancreatitis or episodes of chronic pancreatitis. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include obtaining written consent from participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The trial population was selected based on specific inclusion criteria, ensuring that participants have a documented history of the condition under investigation.

The clinical trial is designed to evaluate the efficacy of **simvastatin** in preventing recurrent pancreatitis. This study is a triple-blind, randomized, controlled trial, ensuring that neither the participants, investigators, nor the data analysts are aware of the treatment assignments. The trial involves two groups: one receiving simvastatin and the other receiving a placebo, specifically **lactose monohydrate**. The trial is set to run for a maximum treatment period of 12 months, with the estimated end date being April 1, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being an adult aged 18 or older, having experienced at least two episodes of acute pancreatitis or chronic pancreatitis, and providing written consent. Following the screening, participants will be randomly assigned to either the simvastatin or placebo group. The primary endpoint is the recurrence of pancreatitis, assessed as a dichotomous variable, while secondary endpoints include the severity of recurrent pancreatitis, new-onset diabetes, and other related health outcomes.

Throughout the trial, participants will attend regular follow-up visits to monitor their health status and adherence to the treatment regimen. These visits will also serve to collect data on any adverse events or changes in health status. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the primary and secondary endpoints. The expected length of participant involvement is up to 12 months, with conditions for early termination including withdrawal of consent, significant adverse events, or non-compliance with the study protocol.

The clinical trial involves the administration of **Simvastatin**, an experimental medication, to evaluate its efficacy in the prevention of recurrent pancreatitis. **Simvastatin** is provided in the form of a film-coated tablet, with a chemical origin. The maximum daily dose is 40 mg, administered orally. The treatment period is set for a maximum of 12 months. Participants are required to adhere to the dosing schedule, and compliance will be monitored throughout the study duration.

In addition to the experimental treatment, a placebo is utilized in the study to serve as a comparator. The placebo is composed of **Lactose Monohydrate**, also in the form of a film-coated tablet. The placebo is chemically derived and administered orally, with a maximum daily dose of 60 mg. The placebo treatment is also scheduled for a maximum period of 12 months. Participant adherence to the placebo regimen will be monitored to ensure compliance and integrity of the trial results.

Efficacy in the clinical trial titled "Simvastatin in the Prevention of Recurrent Pancreatitis, a Triple Blind, Randomized Controlled Trial" will be assessed using both primary and secondary endpoints. The primary endpoint is the **recurrence of pancreatitis**, evaluated as a dichotomous variable. Secondary endpoints include various measures such as recurrences (dichotomous variable), recurrence analyzed through Kaplan-Meier analysis, new-onset diabetes, new-onset exocrine pancreatic insufficiency, severity of recurrent pancreatitis, and the number of days admitted due to recurrent acute pancreatitis (AP). Additionally, the trial will assess the number of visits to the emergency room and admissions due to abdominal pain without meeting criteria for acute pancreatitis, as well as imaging signs of chronic pancreatitis.