Post-ERCP Acute PancreatitisPhase 3INTRONCT05252754
Rectal Indomethacin and Oral Tacrolimus Versus Combination to Prevent Post-ERCP Pancreatitis
A Phase 3 study testing Tacrolimus capsule and Rectal Indomethacin in people with Post-ERCP Acute Pancreatitis, run by Johns Hopkins University at 5 sites in 3 countries.
Trial summary
This research is being done to see if using oral tacrolimus before endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-ERCP Acute Pancreatitis
- What is being tested?
- Tacrolimus capsule and Rectal Indomethacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,874 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 18 Jan 2023to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient who is undergoing endoscopic retrograde cholangiopancreatography (ERCP) at any of the participating centers, is at least 18 years old and provides informed consent can be included in the study.
Who cannot join
- Unwillingness or inability to consent for the study.
- Pregnancy
- Breastfeeding mother
- Chronic calcific pancreatitis
- ERCP for biliary stent exchange or removal
- ERCP in a patient with prior biliary sphincterotomy, but without anticipated pancreatogram.
Show all 14Show fewer
- Biliary intervention in a patient with pancreas divisum.
- Standard contraindications to tacrolimus or NSAID use.
- Current tacrolimus or immune modulator use.
- Chronic kidney disease with glomerular filtration rate (GFR) < 30 or acute kidney injury.
- Absence of rectum.
- Acute pancreatitis within 30 days of ERCP.
- Pancreatic head malignancy.
- Sphincter of Oddi dysfunction (Type 3).
Trial locations and contacts
5 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 3 countries
India3 sites, 3 recruiting
- Not yet recruiting
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
Saroj K, Sinha, sarojksinha@hotmail.com
- Recruiting
Asian Institute of Gastroenterology
Hyderabad, Andhra Pradesh, 500082
Sundeep Lakhtakia, MD, DM, drsundeeplakhtakia@gmail.com
- Not yet recruiting
Apollo Multispecialty Hospitals,
Kolkata, West Bengal, 700054
Mahesh K Goenka, MD, DM, mkgkolkata@gmail.com
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Venkata S Akshintala, M.D., 410-624-6955, vakshin1@jhmi.edu
Singapore1 site, 1 recruiting
- Not yet recruiting
Singapore General Hospital
Singapore, 169608
Clement CH Wu, clement.wu.c.h@singhealth.com.sg
About this study
Official title: A Randomized Trial Comparing Rectal Indomethacin Alone Versus a Combination of Rectal Indomethacin and Oral Tacrolimus for Post-ERCP Pancreatitis Prophylaxis
This research is being done to see if using oral tacrolimus before endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).
Read the detailed description
Background: In the US alone, almost 700,000 endoscopic retrograde cholangiopancreatographies (ERCPs) are performed each year, and the utilization of ERCP over the last 10 years has increased due to the established therapeutic benefit of the procedure. The most common complication of ERCP is the development of post-ERCP pancreatitis (PEP). Depending on whether the ERCP is performed in average or high-risk patients, the incidence of PEP ranges from 3-15%. The average Medicare reimbursement for PEP is approximately $6,000 and the estimated annual cost burden of PEP is in excess of $200 million. Anti-inflammatory prophylaxis with rectal indomethacin and pancreatic duct stenting has been shown to reduce both the incidence of PEP and PEP severity. Yet, PEP remains a common complication due to the suboptimal efficacy of these current preventative modalities. The primary reason for the lack of progress in PEP prophylaxis is the lack of novel approaches to target the underlying mechanisms of PEP.
In the initiation of acute pancreatitis, calcium is released by acinar cells, the main parenchymal cell of the pancreas. Central to this pathway is the activation of the heterodimeric calcium-dependent serine, threonine phosphatase calcineurin (Cn). In addition to experimental evidence, recent clinical reports have demonstrated lower rates of PEP in transplant patients taking Cn inhibitors. To gain an understanding of this phenomenon, the investigators performed a search of the electronic medical records at the University of Pittsburgh Medical Center, from 2005 to 2013, for patients who underwent ERCP and found that tacrolimus users had close to a 50% reduction in PEP rates compared to non-tacrolimus users (13.2% to 6.9%). A recent retrospective study showed similar results. While these observations are subject to several confounders, including co-morbidity and polypharmacy, the overall data provides both an experimental and clinical premise for investigating the efficacy of Cn inhibitors in PEP.
In this trial, the investigators test the overarching hypothesis that tacrolimus, administered as an oral loading bolus just prior to ERCP, will provide additive PEP prophylaxis to the current standard of care, rectal indomethacin.
Hypothesis: H1: A combination of oral tacrolimus and rectal indomethacin is superior to the use of rectal indomethacin alone, for the prevention of post-ERCP pancreatitis among high-risk individuals.
H2: Oral tacrolimus is superior to placebo for the prevention of post-ERCP pancreatitis among non-high-risk individuals.
Sample size justification: Based on the information from the earlier controlled trials, the Investigators assume that the PEP incidence will be 7% in the Rectal Indomethacin group and it will be reduced to 3% by the additional use of oral tacrolimus in combination with rectal indomethacin A two-sided α=0.05, and a power of 0.8, will require 926 patients for the comparison between the combination of oral tacrolimus and rectal indomethacin versus rectal indomethacin alone among high-risk individuals. Since 20% of patients undergoing ERCP are expected to be at high risk based on the investigators' prior experience, the investigators estimate that the total number of patients needed to undergo ERCP is 4630. Adjusting for a 5% drop-out rate, the sample size needed will be 4874.
Recruitment and Consenting: Patients scheduled to undergo ERCP will be screened for patient-based inclusion/exclusion criteria and will be consented to before the start of ERCP.
Randomization: The randomization schedule is centrally generated at Johns Hopkins University. Patients will be stratified by the participating center. Within each stratum randomly varying block sizes of 30-50 will be used. Patients and treating physicians will be blinded for the treatment allocation. This will be ensured by directly delivering the list of randomly generated numbers to the investigational drug pharmacies.
Statistical Plan: The baseline characteristics of age, sex, comorbidity, American Society of Anesthesiologists (ASA) score, ERCP indication, PEP risk factors, and the use of other prophylactics (e.g. Intravenous Fluids) will be reported. Data will be presented in percentages for categorical variables. Continuous variables will be presented as mean with standard deviation (normal distribution) or median with interquartile range (skewed distribution).
The modified intention-to-treat (ITT) principle will be applied to the primary analysis. That is, all randomized patients will be analyzed according to the patients' original treatment allocation, regardless of study protocol violations. The only patients excluded from the analysis will be those in whom the duodenum was not reached and the papilla was not manipulated (e.g., in case of upper gastrointestinal stenosis, aspiration risk, restless patient) or follow-up could not be performed for 5 days. Because these patients will not ultimately undergo an ERCP, there is no risk of PEP. A two-tailed P value of less than 0.05 is considered to be statistically significant.
- Conditions
- Post-ERCP Acute Pancreatitis
- Being tested
- Tacrolimus capsule, Placebo, Rectal Indomethacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus capsuleDrug
Also called Prograf, Protopic
Tacrolimus 5 mg PO, 1-2 hours prior to endoscopy
PlaceboDrug
Placebo PO, 1-2 hours prior to endoscopy.
Rectal IndomethacinDrug
Also called Indocin, NSAIDS
100 mg Rectal Indomethacin immediately after ERCP, in high-risk patients.
| Study group | Role | What they receive |
|---|---|---|
| Oral Tacrolimus + Indomethacin | Experimental | * Tacrolimus Capsule 1-2 hours prior to the endoscopy
* Rectal Indomethacin immediately after ERCP, in high-risk patients Receives: Drug: Tacrolimus capsule; Drug: Rectal Indomethacin |
| Oral Placebo + Indomethacin | Placebo comparator | * Placebo Capsule 1-2 hours prior to the endoscopy
* Rectal Indomethacin immediately after ERCP, in high-risk patients Receives: Drug: Placebo; Drug: Rectal Indomethacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of subjects in each study group with Post ERCP Acute Pancreatitis (PEP)
Incidence of PEP as defined by the consensus guidelines as
- New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis
- Amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure
- Hospitalization or prolongation of existing hospitalization for at least 2 days
Measured: Within 30 days of ERCP
Secondary outcomes (1)
The proportion of subjects in each study group with moderate-severe Post-ERCP Pancreatitis
PEP severity grading will be based on the modified Atlanta Criteria.
- Mild PEP: Hospitalization ≤3 days without organ failure, local or systemic complications.
- Moderate PEP: Hospitalization 4-10 days with transient organ failure that resolves within 48 hours and/or local or systemic complications.
- Severe PEP: Hospitalization >10 days with development of pancreatic necrosis or pseudocyst, persistent (>48 hours) single or multiple organ failure, and/or need for additional endoscopic, percutaneous, or surgical intervention for pancreatitis-related complications.
Measured: Within 30 days of ERCP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2022
- Study start18 Jan 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Post-ERCP Acute PancreatitisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,874 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Venkata S. Akshintala, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05252754
- Sponsor's protocol ID
- IRB00269963
- Acronym
- INTRO
- Status last verified
- Dec 2025
- First submitted
- 14 Feb 2022
- Last updated
- 9 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Coelho-Prabhu N, Shah ND, Van Houten H, Kamath PS, Baron TH. Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort. BMJ Open. 2013 May 31;3(5):e002689. doi: 10.1136/bmjopen-2013-002689.
PubMed 23793659Mazen Jamal M, Yoon EJ, Saadi A, Sy TY, Hashemzadeh M. Trends in the utilization of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. Am J Gastroenterol. 2007 May;102(5):966-75. doi: 10.1111/j.1572-0241.2007.01127.x. Epub 2007 Mar 23.
PubMed 17319932Moffatt DC, Yu BN, Yie W, Bernstein CN. Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over the past 25 years: a population-based study. Gastrointest Endosc. 2014 Apr;79(4):615-22. doi: 10.1016/j.gie.2013.08.028. Epub 2013 Oct 8.
PubMed 24119510Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri G, Ghezzo L, Familiari L, Giardullo N, Mutignani M, Lombardi G, Talamini G, Spadaccini A, Briglia R, Piazzi L; SEIFRED Group. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol. 2010 Aug;105(8):1753-61. doi: 10.1038/ajg.2010.136. Epub 2010 Apr 6.
PubMed 20372116Fan JH, Qian JB, Wang YM, Shi RH, Zhao CJ. Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastroenterol. 2015 Jun 28;21(24):7577-83. doi: 10.3748/wjg.v21.i24.7577.
PubMed 26140006Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2018 Jul 4;18(1):106. doi: 10.1186/s12876-018-0837-4.
PubMed 29973142Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016 Apr;150(4):911-7; quiz e19. doi: 10.1053/j.gastro.2015.12.040. Epub 2016 Jan 9.
PubMed 26775631Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J Biochem. 2002 Jan;131(1):1-15. doi: 10.1093/oxfordjournals.jbchem.a003063.
PubMed 11754729Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. doi: 10.1152/physrev.2000.80.4.1483.
PubMed 11015619Aramburu J, Rao A, Klee CB. Calcineurin: from structure to function. Curr Top Cell Regul. 2000;36:237-95. doi: 10.1016/s0070-2137(01)80011-x. No abstract available.
PubMed 10842755Muili KA, Ahmad M, Orabi AI, Mahmood SM, Shah AU, Molkentin JD, Husain SZ. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury. Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G898-905. doi: 10.1152/ajpgi.00545.2011. Epub 2012 Feb 9.
PubMed 22323127Thiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V, Kochman ML. Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation. Clin Gastroenterol Hepatol. 2020 May;18(5):1224-1232.e1. doi: 10.1016/j.cgh.2019.10.014. Epub 2019 Oct 14.
PubMed 31622734Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995 Dec;29(6):404-30. doi: 10.2165/00003088-199529060-00003.
PubMed 8787947Wen L, Javed TA, Yimlamai D, Mukherjee A, Xiao X, Husain SZ. Transient High Pressure in Pancreatic Ducts Promotes Inflammation and Alters Tight Junctions via Calcineurin Signaling in Mice. Gastroenterology. 2018 Oct;155(4):1250-1263.e5. doi: 10.1053/j.gastro.2018.06.036. Epub 2018 Jun 19.
PubMed 29928898Orabi AI, Wen L, Javed TA, Le T, Guo P, Sanker S, Ricks D, Boggs K, Eisses JF, Castro C, Xiao X, Prasadan K, Esni F, Gittes GK, Husain SZ. Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis. Cell Mol Gastroenterol Hepatol. 2017 Jan;3(1):119-128. doi: 10.1016/j.jcmgh.2016.08.006.
PubMed 28090570
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial Comparing Rectal Indomethacin Alone Versus a Combination of Rectal Indomethacin and Oral Tacrolimus for Post-ERCP Pancreatitis Prophylaxis
- ClinicalTrials.gov ID
- NCT05252754
- Acronym / sponsor ID
- INTRO / IRB00269963
- Conditions
- Post-ERCP Acute Pancreatitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 4,874 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 18 Jan 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 23 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is being done to see if using oral tacrolimus before endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).
Detailed description
Background: In the US alone, almost 700,000 endoscopic retrograde cholangiopancreatographies (ERCPs) are performed each year, and the utilization of ERCP over the last 10 years has increased due to the established therapeutic benefit of the procedure. The most common complication of ERCP is the development of post-ERCP pancreatitis (PEP). Depending on whether the ERCP is performed in average or high-risk patients, the incidence of PEP ranges from 3-15%. The average Medicare reimbursement for PEP is approximately $6,000 and the estimated annual cost burden of PEP is in excess of $200 million. Anti-inflammatory prophylaxis with rectal indomethacin and pancreatic duct stenting has been shown to reduce both the incidence of PEP and PEP severity. Yet, PEP remains a common complication due to the suboptimal efficacy of these current preventative modalities. The primary reason for the lack of progress in PEP prophylaxis is the lack of novel approaches to target the underlying mechanisms of PEP.
In the initiation of acute pancreatitis, calcium is released by acinar cells, the main parenchymal cell of the pancreas. Central to this pathway is the activation of the heterodimeric calcium-dependent serine, threonine phosphatase calcineurin (Cn). In addition to experimental evidence, recent clinical reports have demonstrated lower rates of PEP in transplant patients taking Cn inhibitors. To gain an understanding of this phenomenon, the investigators performed a search of the electronic medical records at the University of Pittsburgh Medical Center, from 2005 to 2013, for patients who underwent ERCP and found that tacrolimus users had close to a 50% reduction in PEP rates compared to non-tacrolimus users (13.2% to 6.9%). A recent retrospective study showed similar results. While these observations are subject to several confounders, including co-morbidity and polypharmacy, the overall data provides both an experimental and clinical premise for investigating the efficacy of Cn inhibitors in PEP.
In this trial, the investigators test the overarching hypothesis that tacrolimus, administered as an oral loading bolus just prior to ERCP, will provide additive PEP prophylaxis to the current standard of care, rectal indomethacin.
Hypothesis: H1: A combination of oral tacrolimus and rectal indomethacin is superior to the use of rectal indomethacin alone, for the prevention of post-ERCP pancreatitis among high-risk individuals.
H2: Oral tacrolimus is superior to placebo for the prevention of post-ERCP pancreatitis among non-high-risk individuals.
Sample size justification: Based on the information from the earlier controlled trials, the Investigators assume that the PEP incidence will be 7% in the Rectal Indomethacin group and it will be reduced to 3% by the additional use of oral tacrolimus in combination with rectal indomethacin A two-sided α=0.05, and a power of 0.8, will require 926 patients for the comparison between the combination of oral tacrolimus and rectal indomethacin versus rectal indomethacin alone among high-risk individuals. Since 20% of patients undergoing ERCP are expected to be at high risk based on the investigators' prior experience, the investigators estimate that the total number of patients needed to undergo ERCP is 4630. Adjusting for a 5% drop-out rate, the sample size needed will be 4874.
Recruitment and Consenting: Patients scheduled to undergo ERCP will be screened for patient-based inclusion/exclusion criteria and will be consented to before the start of ERCP.
Randomization: The randomization schedule is centrally generated at Johns Hopkins University. Patients will be stratified by the participating center. Within each stratum randomly varying block sizes of 30-50 will be used. Patients and treating physicians will be blinded for the treatment allocation. This will be ensured by directly delivering the list of randomly generated numbers to the investigational drug pharmacies.
Statistical Plan: The baseline characteristics of age, sex, comorbidity, American Society of Anesthesiologists (ASA) score, ERCP indication, PEP risk factors, and the use of other prophylactics (e.g. Intravenous Fluids) will be reported. Data will be presented in percentages for categorical variables. Continuous variables will be presented as mean with standard deviation (normal distribution) or median with interquartile range (skewed distribution).
The modified intention-to-treat (ITT) principle will be applied to the primary analysis. That is, all randomized patients will be analyzed according to the patients' original treatment allocation, regardless of study protocol violations. The only patients excluded from the analysis will be those in whom the duodenum was not reached and the papilla was not manipulated (e.g., in case of upper gastrointestinal stenosis, aspiration risk, restless patient) or follow-up could not be performed for 5 days. Because these patients will not ultimately undergo an ERCP, there is no risk of PEP. A two-tailed P value of less than 0.05 is considered to be statistically significant.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Tacrolimus + Indomethacin | Experimental | Drug: Tacrolimus capsule, Drug: Rectal Indomethacin* Tacrolimus Capsule 1-2 hours prior to the endoscopy * Rectal Indomethacin immediately after ERCP, in high-risk patients |
| Oral Placebo + Indomethacin | Placebo comparator | Drug: Placebo, Drug: Rectal Indomethacin* Placebo Capsule 1-2 hours prior to the endoscopy * Rectal Indomethacin immediately after ERCP, in high-risk patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Any patient who is undergoing endoscopic retrograde cholangiopancreatography (ERCP) at any of the participating centers, is at least 18 years old and provides informed consent can be included in the study.
Key exclusion criteria (14 listed)
- Unwillingness or inability to consent for the study.
- Pregnancy
- Breastfeeding mother
- Chronic calcific pancreatitis
- ERCP for biliary stent exchange or removal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus capsuleAlso: Prograf, ProtopicTacrolimus 5 mg PO, 1-2 hours prior to endoscopy | Drug | Oral Tacrolimus + Indomethacin |
| PlaceboPlacebo PO, 1-2 hours prior to endoscopy. | Drug | Oral Placebo + Indomethacin |
| Rectal IndomethacinAlso: Indocin, NSAIDS100 mg Rectal Indomethacin immediately after ERCP, in high-risk patients. | Drug | Oral Placebo + Indomethacin, Oral Tacrolimus + Indomethacin |
Primary outcome
The proportion of subjects in each study group with Post ERCP Acute Pancreatitis (PEP)
Time frame: Within 30 days of ERCP
Incidence of PEP as defined by the consensus guidelines as 1. New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis 2. Amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure 3. Hospitalization or prolongation of existing hospitalization for at least 2 days
1 secondary outcome
The proportion of subjects in each study group with moderate-severe Post-ERCP Pancreatitis
Time frame: Within 30 days of ERCP
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2025.
- Background: PubMed 23793659Coelho-Prabhu N, Shah ND, Van Houten H, Kamath PS, Baron TH. Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort. BMJ Open. 2013 May 31;3(5):e002689. doi: 10.1136/bmjopen-2013-002689.
- Background: PubMed 17319932Mazen Jamal M, Yoon EJ, Saadi A, Sy TY, Hashemzadeh M. Trends in the utilization of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. Am J Gastroenterol. 2007 May;102(5):966-75. doi: 10.1111/j.1572-0241.2007.01127.x. Epub 2007 Mar 23.
- Background: PubMed 24119510Moffatt DC, Yu BN, Yie W, Bernstein CN. Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over the past 25 years: a population-based study. Gastrointest Endosc. 2014 Apr;79(4):615-22. doi: 10.1016/j.gie.2013.08.028. Epub 2013 Oct 8.
- Background: PubMed 20372116Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri G, Ghezzo L, Familiari L, Giardullo N, Mutignani M, Lombardi G, Talamini G, Spadaccini A, Briglia R, Piazzi L; SEIFRED Group. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol. 2010 Aug;105(8):1753-61. doi: 10.1038/ajg.2010.136. Epub 2010 Apr 6.
- Background: PubMed 26140006Fan JH, Qian JB, Wang YM, Shi RH, Zhao CJ. Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastroenterol. 2015 Jun 28;21(24):7577-83. doi: 10.3748/wjg.v21.i24.7577.
- Background: PubMed 29973142Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2018 Jul 4;18(1):106. doi: 10.1186/s12876-018-0837-4.
- Background: PubMed 26775631Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016 Apr;150(4):911-7; quiz e19. doi: 10.1053/j.gastro.2015.12.040. Epub 2016 Jan 9.
- Background: PubMed 11754729Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J Biochem. 2002 Jan;131(1):1-15. doi: 10.1093/oxfordjournals.jbchem.a003063.
- Background: PubMed 11015619Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. doi: 10.1152/physrev.2000.80.4.1483.
- Background: PubMed 10842755Aramburu J, Rao A, Klee CB. Calcineurin: from structure to function. Curr Top Cell Regul. 2000;36:237-95. doi: 10.1016/s0070-2137(01)80011-x. No abstract available.
- Background: PubMed 22323127Muili KA, Ahmad M, Orabi AI, Mahmood SM, Shah AU, Molkentin JD, Husain SZ. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury. Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G898-905. doi: 10.1152/ajpgi.00545.2011. Epub 2012 Feb 9.
- Background: PubMed 31622734Thiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V, Kochman ML. Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation. Clin Gastroenterol Hepatol. 2020 May;18(5):1224-1232.e1. doi: 10.1016/j.cgh.2019.10.014. Epub 2019 Oct 14.
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An European Multi-centre Cohort Study for Unravelling Pharmacokinetic and Genetic Factors Underlying Post-ERCP Pancreatitis
Post-ERCP Acute Pancreatitis
Not yet recruitingPhase 4
Indomethacin for Biliary ERCP Patients
Pancreatitis Biliary, Pancreatitis Acute Biliary
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Venkata S. Akshintala, M.D. principal investigator
Johns Hopkins University
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus capsule and Rectal Indomethacin in people with Post-ERCP Acute Pancreatitis, run by Johns Hopkins University at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in India, United States, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Venkata S. Akshintala, M.D. (+1 (410) 614-6708, vakshin1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of subjects in each study group with Post ERCP Acute Pancreatitis (PEP) (time frame: Within 30 days of ERCP). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05252754, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.