Simvastatin in the Prevention of Recurrent Pancreatitis

NCT ID: NCT04021498

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-29
• Study Completion Date: 2025-03-01

Brief 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

Detailed 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.

Conditions

Pancreatitis Relapsing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Placebo

placebo

1 year

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

Simvastatin

40 mg

1 year

Group Type: EXPERIMENTAL

Simvastatin 40mg

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Brand name: Simvastatin Normon, 40 mg; lactose (brand name: lactosa monohidrato Fagrón)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

OTHER

Sponsor Role: collaborator

Generalitat Valenciana

OTHER

Sponsor Role: collaborator

Enrique de-Madaria

OTHER

Sponsor Role: lead

Responsible Party

Enrique de-Madaria

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Enrique de-Madaria, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Gastroenterology Department, Hospital General Universitario de Alicante, Spain

Locations

Alicante

Alicante, Alicante, Spain

Countries

Spain

References

Cardenas-Jaen K, Vaillo-Rocamora A, Gracia A, Garg PK, Zapater P, Papachristou GI, Singh VK, Wu BU, de-Madaria E. Simvastatin in the Prevention of Recurrent Pancreatitis: Design and Rationale of a Multicenter Triple-Blind Randomized Controlled Trial, the SIMBA Trial. Front Med (Lausanne). 2021 Feb 10;7:494. doi: 10.3389/fmed.2020.00494. eCollection 2020.

Reference Type: DERIVED

PMID: 33644082 (View on PubMed)

Other Identifiers

SIMBA-16

Identifier Type: -

Identifier Source: org_study_id