Ignite Creation Date:
2024-05-06 @ 8:24 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06367322
Status:
COMPLETED
Last Update Posted:
2024-04-16
First Post:
2024-04-06
Brief Title:
Statins and Post-ERCP Acute Pancreatitis Stark Project
Sponsor:
Hospital General Universitario de Alicante
Organization:
Hospital General Universitario de Alicante
Study Overview
Official Title:
Stark Project Statins and Risk of Post-Endoscopic Retrograde Cholangiopancreatography Acute Pancreatitits
Status:
COMPLETED
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Stark
Brief Summary:
Post-endoscopic retrograde cholangiopancrepatography ERCP acute pancreatitis PEAP is a frequent complication of this endoscopic procedure Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis AP Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP but the role of chronic acetylsalicylic acid ASA treatment is unclear The aim of the study is to investigate whether statins and chronic ASA intake are associated with lower risk of PEAP
Detailed Description:
Introduction
Acute Pancreatitis AP is the most frequent complication after ERCP its incidence is around 35-45 Post-ERCP AP PEAP is defined as a clinical pancreatitis new or worsened abdominal pain with amylaselipase at least three times the upper limit of normal at more than 24 hours after the procedure requiring hospital admission or a prolongation of planned admission It is resulting in increased morbidity of patients undergoing this technique and an increased in health spending due to prolonged hospital days and patient needs In this context different strategies have been investigated to prevent PEAP for example rectal NSAIDs indomethacin or diclofenac 100 mg just before or after procedure and pancreatic stents
On the other hand statins are widely used drugs aimed to lower cholesterol blood levels the frequency of statin use may be as high as 50 of men and 36 of women between the ages of 65 years and 74 years in USA The relationship between statins and AP has been controversial In the past it was believed that statins were associated to an increased risk of AP In Data Sheet of different International Drug Agencies we can find their mainly indications hypercholesterolemia mixed dyslipidaemias hereditary hypercholesterolemia and commons adverse effects with reference to acute pancreatitis myopathy rhabdomyolysis hepatitisjaundice acute pancreatitis Besides some studies most of them case series or case reports have associated the use of different statins with drugs induced AP
However recent evidence suggests the opposite Statins could reduce the risk of AP In a retrospective longitudinal cohort study on data from a big health database from California USA with a big population of three millions nine thousand people the incidence of AP among subjects who used simvastatin was significantly lower than who didnt use it 080 080-081100000 consumersday versus 128 127-128 100000 no consumersday crude incidence rate ratio for risk of AP with simvastatin use 0626 95 confidence interval CI 0588-0668 p00001 In this study patients who received simvastatin were more likely to have gallstone-related disorders alcohol dependence or hyper-triglyceridemia compared with the reference population nevertheless risk of AP was significantly reduced with simvastatin use In multivariate analysis simvastatin was independently associated with reduced risk of pancreatitis adjusted RR 029 95CI 027-031 after adjusting for age gender raceethnicity gallstone disorders alcohol dependence smoking and hypertriglyceridemia Similar results were noted with atorvastatin In a Meta-analysis of 21 randomized controlled trials investigating effects of lipid-modifying therapies on cardiovascular events was assessed the relationship between lipid modifying therapies and risk of AP In this study it was concluded that the use of statin therapies was associated with a lower risk of AP RR 079 95CI 065-095 p001 In a case-control study from Denmark it was examined if statins use is associated with increase risk of acute pancreatitis 2576 first-time admitted cases of AP were controlled with 25 817 gender-matched controls from the general population Prescriptions for statins prior to admission with acute pancreatitis or index date among controls were retrieved from prescription databases Its findings speak against a strong causative effect of statins on the risk of acute pancreatitis and speculated about it could indicate a mild protective effect
Some studies even speculate about an improvement in the severity of AP among patients with prior use of statins In a prospective cohort study from Croatia which included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization severe disease was more common in the no-statin group than in statin group 206 vs 87 p0001 and severity markers were also higher in the no-statin group
It isnt clear what is the mechanism by which statins might have a beneficial effect on acute pancreatitis Basic studies suggest that statins could act on a specific anti-inflammatory pathway inhibited them as hypothesize experimental models Statin effect that may be relevant to AP include blockade of the interleukin 6 mediated Janus kinasesignal transducer pathway and up regulation of the unfolded protein response helpful in modulating the endoplasmic reticulum stress response
Based on the above evidence the study hypothesis is that statins consumption is associated to a decreased incidence of PEAP A prospective cohort study is proposed focused on patients undergoing ERCP with the aim to compare the incidence of PEAP among patients consuming statins and those who do not
Material and Methods
Hypothesis Statins consumption decreases incidence of PEAP I Main aim Compare the incidence of PEAP among patients consuming statins and those who do not
II Secondary aims
Investigate the effect of other drugs especially acetylsalicylic acid ASA in the incidence of PEAP
Study the statin mechanism to decrease the incidence of AP
Study the relationship between use of statins and the severity of AP
Design Study International multicentric cohort study observational analytical prospective focused on patients undergoing ERCP with the aim to compare the incidence of PEAP among patients consuming statins any statin and those who do not
Data acquisition
Data were prospectively acquired by researchers from the participating centers After informed consent the patients were interviewed before and immediately after ERCP According to local clinical practice most of the patients were admitted for 24 hours after the procedure to monitor for possible post-ERCP complications including PEAP Patients discharged earlier were instructed to return in case of concerning symptoms persistent abdominal pain nausea vomiting fever gastrointestinal bleeding etc Names and identification data of the patients were not recorded on the electronic case report form in order to ensure confidentiality in accordance with data protection laws Data monitoring was performed by one of the collaborators Demographic and analytical data comorbidities treatments received more specifically statins and ASA pancreatic diseases procedure results and post-procedural complications were collected
Sample calculation
The sample size calculation was based on a presumed 5 incidence of PEAP among non-statin users an expected 13 ratio of statin users to non-users and a 70 decrease of PEAP rate among statin users The alpha-error was set to 005 and beta-error was set to 020 A sample of 1016 patients was accordingly calculated
Statistical analysis
The results are expressed as the mean standard deviation SD median interquartile range IQR or n Normality was assessed by means of the Shapiro-Wilk test For bivariate analysis quantitative variables were compared with qualitative variables by means of the Student t-test and Mann-Whitney U-test for 2 categories or with ANOVAKruskal-Wallis tests for more than 2 categories Qualitative variables were compared with the chi-square test or Fishers exact test if needed Multivariate analysis was performed by means of binary logistic regression Incidence odds ratio OR and adjusted OR aOR were used as measures of the frequency and strength of association and 95 confidence intervals CIs were calculated for OR and aOR Both OR 95 CI and aOR 95 CI were calculated by means of binary logistic regression bivariate and multivariate analysis respectively The multivariate model included those variables that reached statistical significance in the bivariate analysis p 005 those variables considered as definite risk factors of PEAP according to the 2014 ESGE guidelines 1 and the prophylactic measures such as periprocedural rectal administration of diclofenac or indomethacin or placement of a pancreatic stent All statistical tests were 2-tailed and p-values of less than 005 were considered statistically significant
Acute Pancreatitis AP is the most frequent complication after ERCP its incidence is around 35-45 Post-ERCP AP PEAP is defined as a clinical pancreatitis new or worsened abdominal pain with amylaselipase at least three times the upper limit of normal at more than 24 hours after the procedure requiring hospital admission or a prolongation of planned admission It is resulting in increased morbidity of patients undergoing this technique and an increased in health spending due to prolonged hospital days and patient needs In this context different strategies have been investigated to prevent PEAP for example rectal NSAIDs indomethacin or diclofenac 100 mg just before or after procedure and pancreatic stents
On the other hand statins are widely used drugs aimed to lower cholesterol blood levels the frequency of statin use may be as high as 50 of men and 36 of women between the ages of 65 years and 74 years in USA The relationship between statins and AP has been controversial In the past it was believed that statins were associated to an increased risk of AP In Data Sheet of different International Drug Agencies we can find their mainly indications hypercholesterolemia mixed dyslipidaemias hereditary hypercholesterolemia and commons adverse effects with reference to acute pancreatitis myopathy rhabdomyolysis hepatitisjaundice acute pancreatitis Besides some studies most of them case series or case reports have associated the use of different statins with drugs induced AP
However recent evidence suggests the opposite Statins could reduce the risk of AP In a retrospective longitudinal cohort study on data from a big health database from California USA with a big population of three millions nine thousand people the incidence of AP among subjects who used simvastatin was significantly lower than who didnt use it 080 080-081100000 consumersday versus 128 127-128 100000 no consumersday crude incidence rate ratio for risk of AP with simvastatin use 0626 95 confidence interval CI 0588-0668 p00001 In this study patients who received simvastatin were more likely to have gallstone-related disorders alcohol dependence or hyper-triglyceridemia compared with the reference population nevertheless risk of AP was significantly reduced with simvastatin use In multivariate analysis simvastatin was independently associated with reduced risk of pancreatitis adjusted RR 029 95CI 027-031 after adjusting for age gender raceethnicity gallstone disorders alcohol dependence smoking and hypertriglyceridemia Similar results were noted with atorvastatin In a Meta-analysis of 21 randomized controlled trials investigating effects of lipid-modifying therapies on cardiovascular events was assessed the relationship between lipid modifying therapies and risk of AP In this study it was concluded that the use of statin therapies was associated with a lower risk of AP RR 079 95CI 065-095 p001 In a case-control study from Denmark it was examined if statins use is associated with increase risk of acute pancreatitis 2576 first-time admitted cases of AP were controlled with 25 817 gender-matched controls from the general population Prescriptions for statins prior to admission with acute pancreatitis or index date among controls were retrieved from prescription databases Its findings speak against a strong causative effect of statins on the risk of acute pancreatitis and speculated about it could indicate a mild protective effect
Some studies even speculate about an improvement in the severity of AP among patients with prior use of statins In a prospective cohort study from Croatia which included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization severe disease was more common in the no-statin group than in statin group 206 vs 87 p0001 and severity markers were also higher in the no-statin group
It isnt clear what is the mechanism by which statins might have a beneficial effect on acute pancreatitis Basic studies suggest that statins could act on a specific anti-inflammatory pathway inhibited them as hypothesize experimental models Statin effect that may be relevant to AP include blockade of the interleukin 6 mediated Janus kinasesignal transducer pathway and up regulation of the unfolded protein response helpful in modulating the endoplasmic reticulum stress response
Based on the above evidence the study hypothesis is that statins consumption is associated to a decreased incidence of PEAP A prospective cohort study is proposed focused on patients undergoing ERCP with the aim to compare the incidence of PEAP among patients consuming statins and those who do not
Material and Methods
Hypothesis Statins consumption decreases incidence of PEAP I Main aim Compare the incidence of PEAP among patients consuming statins and those who do not
II Secondary aims
Investigate the effect of other drugs especially acetylsalicylic acid ASA in the incidence of PEAP
Study the statin mechanism to decrease the incidence of AP
Study the relationship between use of statins and the severity of AP
Design Study International multicentric cohort study observational analytical prospective focused on patients undergoing ERCP with the aim to compare the incidence of PEAP among patients consuming statins any statin and those who do not
Data acquisition
Data were prospectively acquired by researchers from the participating centers After informed consent the patients were interviewed before and immediately after ERCP According to local clinical practice most of the patients were admitted for 24 hours after the procedure to monitor for possible post-ERCP complications including PEAP Patients discharged earlier were instructed to return in case of concerning symptoms persistent abdominal pain nausea vomiting fever gastrointestinal bleeding etc Names and identification data of the patients were not recorded on the electronic case report form in order to ensure confidentiality in accordance with data protection laws Data monitoring was performed by one of the collaborators Demographic and analytical data comorbidities treatments received more specifically statins and ASA pancreatic diseases procedure results and post-procedural complications were collected
Sample calculation
The sample size calculation was based on a presumed 5 incidence of PEAP among non-statin users an expected 13 ratio of statin users to non-users and a 70 decrease of PEAP rate among statin users The alpha-error was set to 005 and beta-error was set to 020 A sample of 1016 patients was accordingly calculated
Statistical analysis
The results are expressed as the mean standard deviation SD median interquartile range IQR or n Normality was assessed by means of the Shapiro-Wilk test For bivariate analysis quantitative variables were compared with qualitative variables by means of the Student t-test and Mann-Whitney U-test for 2 categories or with ANOVAKruskal-Wallis tests for more than 2 categories Qualitative variables were compared with the chi-square test or Fishers exact test if needed Multivariate analysis was performed by means of binary logistic regression Incidence odds ratio OR and adjusted OR aOR were used as measures of the frequency and strength of association and 95 confidence intervals CIs were calculated for OR and aOR Both OR 95 CI and aOR 95 CI were calculated by means of binary logistic regression bivariate and multivariate analysis respectively The multivariate model included those variables that reached statistical significance in the bivariate analysis p 005 those variables considered as definite risk factors of PEAP according to the 2014 ESGE guidelines 1 and the prophylactic measures such as periprocedural rectal administration of diclofenac or indomethacin or placement of a pancreatic stent All statistical tests were 2-tailed and p-values of less than 005 were considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None