Simvastatin in the Prevention of Recurrent Pancreatitis
Simvastatin in the Prevention of Recurrent Pancreatitis
Recurrent acute pancreatitis and recurrent relapses of inflammation in chronic pancreatitis
 are an important problem. In some cases, prevention of these acute flares of inflammation is
 not possible. Population-based studies and meta-analysis of randomized controlled trials
 suggest that statins may decrease the incidence of acute pancreatitis. SIMBA aims to
 investigate the effect of simvastatin on the incidence of new episodes of pancreatitis in
 recurrent acute pancreatitis and chronic pancreatitis. This is a non-profit,
 researcher-driven placebo-controlled multicenter (27 Spanish centers) randomized controlled
 trial
Acute pancreatitis (AP) is the 3rd cause of hospital admission due to gastrointestinal
 disease. Approximately 20% of the patients will relapse after a first episode of AP. The low
 frequency of relapse in biliary AP is due to the high effectiveness of cholecystectomy but a
 first episode of AP due to alcoholic or other etiologies is associated with relapse in one
 every four patients. Currently, besides counselling for alcohol and tobacco abstinence, there
 is no specific medical treatment that changes the natural history of recurrent AP. Recurrent
 AP is an intermediary stage in the pathogenesis of chronic pancreatitis (CP) and a subset of
 recurrent AP patients during their natural course transition to CP (one every three
 patients). Forty-five percent of patients with CP experience intermittent flares of pain.
 Simvastatin has been associated to a decrease in the incidence of AP in a population-based
 study (Wu et al, Gut. 2015) and in a meta-analysis of randomized controlled trials (Preiss et
 al, JAMA 2012).

 The main aim of SIMBA (SIMvastatin in the prevention of recurrent pancreatitis, a triple
 Blind rAndomized controlled multicenter trial) is to compare the recurrence rate of
 pancreatitis in patients with established recurrent pancreatitis (acute pancreatitis and
 acute flares in chronic pancreatitis) consuming simvastatin versus placebo.

 The secondary aims are 1) to compare in patients with recurrent AP at the end of follow-up
 period the progression to chronic pancreatitis on imaging (calcifications and/or dilated
 ductal system), as well as endocrine and exocrine pancreatic function; 2) to compare the
 severity of recurrent pancreatitis between both treatment arms.

 Design: SIMBA is a triple-blind randomized placebo-controlled, parallel-group, superiority
 multicenter (27 Spanish centers) trial. This final protocol (version 4) was finished on June
 20th 2018.
Inclusion Criteria:

 1. Adult (>=18) patients

 2. At least 2 episodes of acute pancreatitis or acute flares of chronic pancreatitis

 3. Written consent to participate in the study

 Exclusion Criteria:

 1. <2 episodes of pancreatitis in the last 12 months.

 2. Statin consumption in the previous year.

 3. Contraindications to the use of Statins

 4. Cholelithiasis or choledocholitiasis diagnosed in the last episode of pancreatitis

 5. Endoscopic sphyncterotomy 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.

 6. 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 less than 1 year

 7. Primary hyperparathyroidism that has been operated between last episode of
 pancreatitis and recruitment or will be operated in less than 1 year

 8. Iatrogenic Pancreatitis

 9. Abstinence syndrome due to alcohol or drugs and/or delirium tremens in the last 6
 months before recruitment

 10. 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

 11. Pregnancy, breastfeeding