Simvastatin in the Prevention of Recurrent Pancreatitis

Pancreatitis Relapsing Clinical Trial

— SIMBA-16  

Official title:

Simvastatin in the Prevention of Recurrent Pancreatitis, a Triple Blind, Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04021498
• Other study ID #: SIMBA-16
• Status: Recruiting
• Phase: Phase 3
• Start date: September 29, 2017
• Est. completion date: September 28, 2022

Study information

• Verified date: September 2019
• Source: Hospital General Universitario de Alicante
• Contact: Alicia Vaillo
• Phone: 0034 965933468
• Email: vailloalicia[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: September 28, 2022
• Est. primary completion date: July 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis Relapsing
• Pancreatitis, Chronic

Intervention

Drug:
• Simvastatin 40mg
phase III, triple-blind randomised placebo-controlled trial comparing simvastatin 40 mg/day versus placebo (lactose). One hundred and fifty eight patients with recurrent AP (at least 2 episodes) will be included (79 per arm of treatment). Treatment and follow-up will last for 12 months.

Other:
• Placebo
phase III, triple-blind randomised placebo-controlled trial comparing simvastatin 40 mg/day versus placebo (lactose). One hundred and fifty eight patients with recurrent AP (at least 2 episodes) will be included (79 per arm of treatment). Treatment and follow-up will last for 12 months.

Locations

Country	Name	City	State
Spain	Alicante	Alicante

Sponsors (4)

Lead Sponsor	Collaborator
Enrique de-Madaria	Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Generalitat Valenciana, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary end point	Recurrence of pancreatitis during the follow-up period. Pancreatitis is defined as 2 or more of the following criteria: I) increased amylase and/or lipase in blood higher than 3 times the upper limit of normality, II) typical abdominal pain and III) signs of acute pancreatitis or acute flare of inflammation in chronic pancreatitis on imaging (CT scan or MRI).	1 year
Secondary	Secondary end point	New-onset diabetes at the end of follow-up, according to the American Diabetes Association criteria. Blood levels of glycosylated hemoglobin at the end of follow-up will also be compared to baseline (beginning of the study)	1 year
Secondary	New-onset exocrine pancreatic insufficiency	New-onset exocrine pancreatic insufficiency defined by fecal elastase-1 <100 mcg/g. Fecal elastase-1 levels at the end of follow-up will also be compared to baseline	1 year
Secondary	Chronic Pancreatitis on imaging	Chronic Pancreatitis on imaging at the end of follow-up, defined as calcifications and/or dilated pancreatic duct (=4mm) on a CT scan	1 year
Secondary	All-cause hospital admissions	Frequency of all-cause hospital admissions	1 year
Secondary	Severity of pancreatitis	Severity of pancreatitis according to the revision of the Atlanta Classification (moderate-to-severe versus mild)	1 year
Secondary	Adherence to treatment	Percentage of the planned treatment consumed by the patient	1 year
Secondary	Adverse events	Frequency of adverse events	1 year