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Simvastatin in the Prevention of Recurrent Pancreatitis (SIMBA-16)

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ClinicalTrials.gov Identifier: NCT04021498
Recruitment Status : Recruiting
First Posted : July 16, 2019
Last Update Posted : September 24, 2019
Sponsor:
Collaborators:
Instituto de Salud Carlos III
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Generalitat Valenciana
Information provided by (Responsible Party):
Enrique de-Madaria, Hospital General Universitario de Alicante

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

Condition or disease Intervention/treatment Phase
Pancreatitis Relapsing Drug: Simvastatin 40mg Other: Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Simvastatin in the Prevention of Recurrent Pancreatitis, a Triple Blind, Randomized Controlled Trial
Actual Study Start Date : September 29, 2017
Estimated Primary Completion Date : July 29, 2022
Estimated Study Completion Date : September 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatitis
Drug Information available for: Simvastatin

Arm Intervention/treatment
Placebo Comparator: Placebo

placebo

1 year

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.
Other Name: lactose (brand name: lactosa monohidrato Fagrón)

Experimental: Simvastatin

40 mg

1 year

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 Name: Brand name: Simvastatin Normon, 40 mg




Primary Outcome Measures :
  1. Primary end point [ Time Frame: 1 year ]
    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).


Secondary Outcome Measures :
  1. Secondary end point [ Time Frame: 1 year ]
    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)

  2. New-onset exocrine pancreatic insufficiency [ Time Frame: 1 year ]
    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

  3. Chronic Pancreatitis on imaging [ Time Frame: 1 year ]
    Chronic Pancreatitis on imaging at the end of follow-up, defined as calcifications and/or dilated pancreatic duct (≥4mm) on a CT scan

  4. All-cause hospital admissions [ Time Frame: 1 year ]
    Frequency of all-cause hospital admissions

  5. Severity of pancreatitis [ Time Frame: 1 year ]
    Severity of pancreatitis according to the revision of the Atlanta Classification (moderate-to-severe versus mild)

  6. Adherence to treatment [ Time Frame: 1 year ]
    Percentage of the planned treatment consumed by the patient

  7. Adverse events [ Time Frame: 1 year ]
    Frequency of adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04021498


Contacts
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Contact: Alicia Vaillo 0034 965933468 vailloalicia@gmail.com

Locations
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Spain
Alicante Recruiting
Alicante, Spain, 03010
Contact: Alicia Vaillo    0034 965933468    vailloalicia@gmail.com   
Sponsors and Collaborators
Enrique de-Madaria
Instituto de Salud Carlos III
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Generalitat Valenciana
Investigators
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Principal Investigator: Enrique de-Madaria, MD PhD Gastroenterology Department, Hospital General Universitario de Alicante, Spain

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Responsible Party: Enrique de-Madaria, Principal Investigator, Hospital General Universitario de Alicante
ClinicalTrials.gov Identifier: NCT04021498     History of Changes
Other Study ID Numbers: SIMBA-16
First Posted: July 16, 2019    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Enrique de-Madaria, Hospital General Universitario de Alicante:
Pancreatitis
Acute pancreatitis
Chronic pancreatitis
Simvastatin
Recurrent
Additional relevant MeSH terms:
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Pancreatitis
Pancreatitis, Chronic
Pancreatic Diseases
Digestive System Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors