Post-ERCP Acute PancreatitisPhase 3IND+LRPEPNCT02641561
Lactated Ringers With or Without Rectal Indomethacin to Prevent Post-ERCP Pancreatitis
A Phase 3 study testing Indomethacin, Lactated Ringer's Solution and Normal Saline in people with Post-ERCP Acute Pancreatitis, run by The Cooper Health System at 1 site in United States.
Trial summary
Post-ERCP pancreatitis is a well-known and sometimes life-threatening complication of ERCP. Both LR and rectal indomethacin have shown benefit in preventing post-ERCP pancreatitis. Despite this, no study to date has evaluated both of these measures for preventing post-ERCP pancreatitis. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Post-ERCP Acute Pancreatitis
- What is being tested?
- Indomethacin, Lactated Ringer's Solution and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Jun 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1 Subjects who are undergoing endoscopic retrograde cholangiopancreatography (ERCP)
- Age > 18 years
- Non-pregnant
- Non-prisoners
- Subjects who can sign informed consent
- Serum Creatinine < 1.2 milligrams/deciliter (mg/dL)
Show all 11Show fewer
- Subjects without renal failure (acute or chronic)
- Subjects without congestive heart failure (ejection fraction < 40%)
- Subjects without cirrhosis of the liver
- Subjects without allergy to aspirin or non-steroidal anti-inflammatory drugs (NSAIDS)
- Subjects not on non-steroidal anti-inflammatory drugs NSAIDS prior to enrollment
Who cannot join
- Subjects who are not undergoing ERCP
- Age < 18 years
- Pregnancy
- Prisoners
- Subjects lacking the capacity to consent for themselves
- Serum Creatinine > 1.2 milligrams/deciliter (mg/dL)
Show all 13Show fewer
- Subjects with renal failure (acute and chronic)
- Subjects with congestive heart failure (ejection fraction < 40%)
- Subjects with cirrhosis of the liver
- Subjects with allergy to aspirin or non-steroidal anti-inflammatory drugs (NSAIDS)
- Subjects with gastrointestinal hemorrhage
- Subjects on chronic non-steroidal anti-inflammatory drugs NSAIDS
- Subjects with acute pancreatitis the day of their procedure (CITE 1-3)(APPENDIX 1)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prevention of Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) - Induced Pancreatitis Using Aggressive Lactated Ringer's Infusion and/or Rectal Indomethacin
Post-ERCP pancreatitis is a well-known and sometimes life-threatening complication of ERCP. Both LR and rectal indomethacin have shown benefit in preventing post-ERCP pancreatitis. Despite this, no study to date has evaluated both of these measures for preventing post-ERCP pancreatitis. It is our hope to evaluate the combination of these two modalities for preventing post-ERCP pancreatitis compared with either modality alone.
Read the detailed description
Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used diagnostic and therapeutic intervention used in Gastroenterology. At Cooper University Hospital (CUH), we perform approximately 700 ERCPs per year. A known complication of ERCP is post-ERCP pancreatitis. The incidence of post-ERCP pancreatitis has been cited at anywhere from 2.6-3.5% of cases. Also, severe acute pancreatitis has been cited at rates of 0.32-0.4% and death 0.11%.
Recent literature has cited the use of several modalities useful in preventing post-ERCP pancreatitis. Among the modalities evaluated non-steroidal anti-inflammatory drugs (NSAIDS), specifically rectal indomethacin, have demonstrated benefit in preventing post-ERCP. In particular Elmunzer et al demonstrated a benefit in those with sphincter of oddi dysfunction (SOD) and those deemed "high risk" for post-ERCP pancreatitis. Other medication such at octreotoide and corticosteroid have shown mixed results.
Additionally, recent studies have demonstrated the use of lactated ringer's solution (LR) in lieu of normal saline (NS) in patient's with acute pancreatitis. Due to this thought process a recent study evaluated the use of LR in preventing post-ERCP pancreatitis. The results of this study showed that no patients who received aggressive LR hydration developed post-ERCP pancreatitis.
As rectal indomethacin and LR infusion appear to have the most definitive evidence for preventing post-ERCP pancreatitis, it is our hope to evaluate the combination of these two therapies for the prevention of post-ERCP pancreatitis.
This is a double blinded, randomized prospective cohort study involving 4 treatment groups undergoing ERCP.
All treatment arms shall receive consent, pre-procedural risk stratification, demographic data and pre-procedural liker pain scale. All subjects shall receive a study subject number and undergo randomization. All subjects also will receive post-procedural likert pain scale assessment, day 1 and 30 questioning. Treatment arms shall be separated into whether subjects are high risk or not defined in.
Time 0 (Visit 1):
Subjects undergo standard pre-procedural evaluation by nursing, anesthesia and consent for procedure/anesthesia.
The subject shall then be evaluated for study participation and subsequently consented if they desire to be part of the study. They may also undergo informed consent prior to the day of their procedure during their normal office visit. All subjects must have Liver function tests (LFTs), amylase and lipase levels drawn prior to their ERCP test. Subjects will be excluded from study participation if they have acute pancreatitis defined as;
The diagnosis of AP is most often established by the presence of 2 of the 3 following criteria:
(i) abdominal pain consistent with the disease (ii) serum amylase and / or lipase greater than three times the upper limit of normal, and / or (iii) characteristic findings from abdominal imaging
The day of their procedure, nursing shall then obtain intravenous peripheral access (standard for ERCP). Initial demographic data and risk factor data shall be obtained. Subjects shall then be randomized to one of the four study arms and given a study number randomly generated:
Pending which treatment arm the patient is enrolled into the subject shall then receive the above listed therapies and undergo their procedure.
Post-procedure the interventions performed during the ERCP shall be recorded and the patient will go through the standard recovery process. Post-procedure after recovery from anesthesia, the patients shall then be evaluated for the presence of pain after ERCP testing on the standard likert pain scale.
If the subject's pain has substantially increased from baseline, subjects shall then be admitted to the hospital and LFTs, a lipase and amylase level shall be drawn and abdominal imaging ordered if needed by the admitting physician (all the standard of care).
Time 1 Days (Visit 2 via phone):
Subjects shall be called 24 hours from ERCP to assess;
- Presence/absence of pain
- If pain, the severity
- Performance of amylase and lipase
- Whether admission, urgent care or emergency department visit did occur
Time 1-30 Days The investigator will await the subjects laboratory values and if > 3 times the upper limit of normal contact the subject via phone.
Time 30 Days (Visit 3 via phone):
Subjects shall be contacted via phone 30 days from ERCP to assess;
- Presence/absence of pain
- If pain, the severity
- Whether admission, urgent care or Emergency Department (ED) visit did occur to a healthcare facility
- Study summary
To detect a difference of 0.24 vs 0.05 a minimum of 48 per group would be needed (using p=0.05).
Descriptive statistics will be used to summarize demographic variables such as age, gender, race, length of stay, as well diagnosis and disease characteristics such as reasons for ERCP, disease intervention, pain,and outcome variables. Data tables will be generated for those variables with means, standard deviation (SD), medians, interquartile range (IQR), and confidence interval (CI). The Chi-Square test will be used to determine the main effect of treatment on ERCP induced pancreatitis. Nonparametric tests will be used to analyze categorical data while normally distributed data will be analyzed using ANOVA to look for treatment effect on other variables of interest.
Binary and Multinomial Logistic Regression will be used to examine predictors of outcome within treatments and across treatments by building interactions into the model (e.g. reasons for ERCP, intervention type). Data analysis will be performed using Systat version 13 and SPSS version 22. A p<0.05 will be considered statistically significant.
- Conditions
- Post-ERCP Acute Pancreatitis
- Being tested
- Indomethacin, Lactated Ringer's Solution, Normal Saline, Placebo
- Keywords
- Pancreatitis, ERCP, Indomethacin, Lactated ringer's
- Medical subject headings
- Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IndomethacinDrug
Also called IND
Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) which is commonly used to reduce inflammation caused by gout, osteoarthritis and rheumatoid arthritis. It acts by blocking the cyclo-oxygenase 1 and 2 (COX) receptors. It has also been implicated to prevent post-ERCP pancreatitis
Lactated Ringer's SolutionDrug
Also called LR
Lactated ringer's solution (LR), is an intravenous fluid (IVF) used commonly during endoscopic procedures and operative procedures. It's composition is similar to that of humans including sodium, chloride, potassium, calcium and lactate. Studies have implicated the use of this fluid in pancreatitis treatment and prevention of post-ERCP pancreatitis
Normal SalineDrug
Also called NS
standard IVF would include 0.9% normal saline (NS) solution used during all endoscopic procedures. 0.9% NS includes equal parts sodium and chloride.
PlaceboDrug
Placebo would be a suppository 50 mg x 2
| Study group | Role | What they receive |
|---|---|---|
| A (NS+Placebo) | Placebo comparator | Normal Saline (intravenous during procedure) + Placebo (100mg suppository per rectum prior to procedure ) Receives: Drug: Normal Saline; Drug: Placebo |
| B (NS+IND) | Active comparator | Normal Saline (intravenous during procedure) + Indomethacin (100mg suppository per rectum prior to procedure ) Receives: Drug: Indomethacin; Drug: Normal Saline |
| C (LR+Placebo) | Active comparator | Lactated ringer's solution (1 Liter, intravenous prior to procedure) + Placebo (100mg suppository per rectum prior to procedure) Receives: Drug: Lactated Ringer's Solution; Drug: Placebo |
| D (LR+IND) | Experimental | Lactated ringer's solution (1 Liter, intravenous prior to procedure) + Indomethacin (100mg suppository per rectum prior to procedure) Receives: Drug: Indomethacin; Drug: Lactated Ringer's Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Either Elevated Amylase or Lipase 3 x Upper Limit of Normal
amylase or lipase
Measured: 30 days after ERCP
The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Imaging Suggestive of Acute Pancreatitis
Imaging may include Computer Tomography
Measured: 30 days after ERCP
Secondary outcomes (18)
The Number of Participants With Acute Respiratory Distress Syndrome (ARDS) After ERCP as Assessed by ARDSnet Criterion (Below)
bilateral opacities on chest imaging not explained by other lung pathology, respiratory failure not explained by heart failure or volume, and overload and a pulmonary arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio under 300, PaO2/FiO2 ratio is the partial pressure arterial oxygen and fraction of inspired oxygen
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Heart rate > 90 beats per minutes
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Respiratory rate > 20 breaths per minute
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
PaCO2 < 4.3 kilopascal (kPa) (32 mmHg)
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Temperature < 36°C(96.8°F) or > 38°C(100.4°F)
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
white blood cell (WBC) count < 4000 cells/mm³ (4 x 109 cells/L)
Measured: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
> 10% immature neutrophils (band forms).
Measured: 30 days after ERCP
The Number of Participants With Sepsis After ERCP as Assessed by Infectious Source Defined by Positive Microbiology Culture
positive blood culture
Measured: 30 days after ERCP
The Number of Participants With Multiple Organ Failure (MOF) After ERCP as Assessed by Elevated Creatinine Blood Test
creatinine > 1.5 milligrams/deciliter (mg/dL)
Measured: 30 days after ERCP
The Number of Participants With Multiple Organ Failure (MOF) After ERCP as Assessed by Elevated International Normalized Ratio (INR)
INR > 1.5
Measured: 30 days after ERCP
The Number of Participants With Pancreatic Pseudocyst After ERCP as Assessed by Abdominal Imaging Suggestive of Pseudocyst
Imaging may include Computer Tomography
Measured: 30 days after ERCP
The Number of Participants With Pancreatic Abscess After ERCP as Assessed by Abdominal Imaging Suggestive of Pancreatic Abscess
Imaging may include Computer Tomography
Measured: 30 days after ERCP
The Number of Participants With Perforation After ERCP as Assessed by Abdominal Imaging Suggestive of Perforation
Imaging may include Computer Tomography
Measured: 30 days after ERCP
The Number of Participants Who Undergo Surgery After ERCP, as Assessed by Surgical Operative Report
Measured: 30 days after ERCP
The Number of Participants With Mortality After ERCP as Assessed by Medical Record Reporting
Measured: 30 days after ERCP
The Number of Participants With Post-procedural Medical Care (ED Visit, Urgent Care, Hospitalization) as Assessed by Medical Record and Patients Self-reporting
Measured: 30 days after ERCP
The Length of Stay (LOS) of Participants After ERCP if Medical Care is Sought as Assessed in Days
Measured: 30 days after ERCP
The Number of Participants Who Were Readmitted After ERCP as Assessed by Medical Record and Patients Self-reporting
Measured: 30 days after ERCP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study startOct 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Post-ERCP Acute PancreatitisStudies of the same condition, open and under way.
- 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
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cooper Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shaffer R S Mok, The Cooper Health System
- Investigators
- Shaffer RS Mok, MD, MBS, Principal investigator, The Cooper Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641561
- Sponsor's protocol ID
- 14-091
- Acronym
- IND+LRPEP
- Status last verified
- Jan 2018
- First submitted
- 5 Nov 2015
- Last updated
- 27 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991 May-Jun;37(3):383-93. doi: 10.1016/s0016-5107(91)70740-2.
PubMed 2070995ASGE Standards of Practice Committee; Anderson MA, Fisher L, Jain R, Evans JA, Appalaneni V, Ben-Menachem T, Cash BD, Decker GA, Early DS, Fanelli RD, Fisher DA, Fukami N, Hwang JH, Ikenberry SO, Jue TL, Khan KM, Krinsky ML, Malpas PM, Maple JT, Sharaf RN, Shergill AK, Dominitz JA. Complications of ERCP. Gastrointest Endosc. 2012 Mar;75(3):467-73. doi: 10.1016/j.gie.2011.07.010. No abstract available.
PubMed 22341094Petersen BT. ERCP outcomes: defining the operators, experience, and environments. Gastrointest Endosc. 2002 Jun;55(7):953-8. doi: 10.1067/mge.2002.123622. No abstract available.
PubMed 12024166Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013 Sep;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218. Epub 2013 Jul 30.
PubMed 23896955Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007 Aug;102(8):1781-8. doi: 10.1111/j.1572-0241.2007.01279.x. Epub 2007 May 17.
PubMed 17509029Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson ML, Williamson PR, Lombard M. Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy. 2007 Sep;39(9):793-801. doi: 10.1055/s-2007-966723.
PubMed 17703388Wang P, Li ZS, Liu F, Ren X, Lu NH, Fan ZN, Huang Q, Zhang X, He LP, Sun WS, Zhao Q, Shi RH, Tian ZB, Li YQ, Li W, Zhi FC. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol. 2009 Jan;104(1):31-40. doi: 10.1038/ajg.2008.5.
PubMed 19098846Ding X, Chen M, Huang S, Zhang S, Zou X. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012 Dec;76(6):1152-9. doi: 10.1016/j.gie.2012.08.021.
PubMed 23164513Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.
PubMed 22494121di Sant'Agnese PA, de Mesy Jensen KL, Churukian CJ, Agarwal MM. Human prostatic endocrine-paracrine (APUD) cells. Distributional analysis with a comparison of serotonin and neuron-specific enolase immunoreactivity and silver stains. Arch Pathol Lab Med. 1985 Jul;109(7):607-12.
PubMed 2409946Elmunzer BJ, Waljee AK, Elta GH, Taylor JR, Fehmi SM, Higgins PD. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut. 2008 Sep;57(9):1262-7. doi: 10.1136/gut.2007.140756. Epub 2008 Mar 28.
PubMed 18375470Murray B, Carter R, Imrie C, Evans S, O'Suilleabhain C. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology. 2003 Jun;124(7):1786-91. doi: 10.1016/s0016-5085(03)00384-6.
PubMed 12806612Rome Foundation. Guidelines--Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. J Gastrointestin Liver Dis. 2006 Sep;15(3):307-12. No abstract available.
PubMed 17203570Prajapati DN, Hogan WJ. Sphincter of Oddi dysfunction and other functional biliary disorders: evaluation and treatment. Gastroenterol Clin North Am. 2003 Jun;32(2):601-18. doi: 10.1016/s0889-8553(03)00025-6.
PubMed 12858608Sherman S, Blaut U, Watkins JL, Barnett J, Freeman M, Geenen J, Ryan M, Parker H, Frakes JT, Fogel EL, Silverman WB, Dua KS, Aliperti G, Yakshe P, Uzer M, Jones W, Goff J, Earle D, Temkit M, Lehman GA. Does prophylactic administration of corticosteroid reduce the risk and severity of post-ERCP pancreatitis: a randomized, prospective, multicenter study. Gastrointest Endosc. 2003 Jul;58(1):23-9. doi: 10.1067/mge.2003.307.
PubMed 12838216
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) - Induced Pancreatitis Using Aggressive Lactated Ringer's Infusion and/or Rectal Indomethacin
- ClinicalTrials.gov ID
- NCT02641561
- Acronym / sponsor ID
- IND+LRPEP / 14-091
- Conditions
- Post-ERCP Acute Pancreatitis
- Keywords
- Pancreatitis, ERCP, Indomethacin, Lactated ringer's
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- The Cooper Health SystemUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Posted 27 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Post-ERCP pancreatitis is a well-known and sometimes life-threatening complication of ERCP. Both LR and rectal indomethacin have shown benefit in preventing post-ERCP pancreatitis. Despite this, no study to date has evaluated both of these measures for preventing post-ERCP pancreatitis. It is our hope to evaluate the combination of these two modalities for preventing post-ERCP pancreatitis compared with either modality alone.
Detailed description
Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used diagnostic and therapeutic intervention used in Gastroenterology. At Cooper University Hospital (CUH), we perform approximately 700 ERCPs per year. A known complication of ERCP is post-ERCP pancreatitis. The incidence of post-ERCP pancreatitis has been cited at anywhere from 2.6-3.5% of cases. Also, severe acute pancreatitis has been cited at rates of 0.32-0.4% and death 0.11%.
Recent literature has cited the use of several modalities useful in preventing post-ERCP pancreatitis. Among the modalities evaluated non-steroidal anti-inflammatory drugs (NSAIDS), specifically rectal indomethacin, have demonstrated benefit in preventing post-ERCP. In particular Elmunzer et al demonstrated a benefit in those with sphincter of oddi dysfunction (SOD) and those deemed "high risk" for post-ERCP pancreatitis. Other medication such at octreotoide and corticosteroid have shown mixed results.
Additionally, recent studies have demonstrated the use of lactated ringer's solution (LR) in lieu of normal saline (NS) in patient's with acute pancreatitis. Due to this thought process a recent study evaluated the use of LR in preventing post-ERCP pancreatitis. The results of this study showed that no patients who received aggressive LR hydration developed post-ERCP pancreatitis.
As rectal indomethacin and LR infusion appear to have the most definitive evidence for preventing post-ERCP pancreatitis, it is our hope to evaluate the combination of these two therapies for the prevention of post-ERCP pancreatitis.
This is a double blinded, randomized prospective cohort study involving 4 treatment groups undergoing ERCP.
All treatment arms shall receive consent, pre-procedural risk stratification, demographic data and pre-procedural liker pain scale. All subjects shall receive a study subject number and undergo randomization. All subjects also will receive post-procedural likert pain scale assessment, day 1 and 30 questioning. Treatment arms shall be separated into whether subjects are high risk or not defined in.
Time 0 (Visit 1):
Subjects undergo standard pre-procedural evaluation by nursing, anesthesia and consent for procedure/anesthesia.
The subject shall then be evaluated for study participation and subsequently consented if they desire to be part of the study. They may also undergo informed consent prior to the day of their procedure during their normal office visit. All subjects must have Liver function tests (LFTs), amylase and lipase levels drawn prior to their ERCP test. Subjects will be excluded from study participation if they have acute pancreatitis defined as;
The diagnosis of AP is most often established by the presence of 2 of the 3 following criteria:
(i) abdominal pain consistent with the disease (ii) serum amylase and / or lipase greater than three times the upper limit of normal, and / or (iii) characteristic findings from abdominal imaging
The day of their procedure, nursing shall then obtain intravenous peripheral access (standard for ERCP). Initial demographic data and risk factor data shall be obtained. Subjects shall then be randomized to one of the four study arms and given a study number randomly generated:
Pending which treatment arm the patient is enrolled into the subject shall then receive the above listed therapies and undergo their procedure.
Post-procedure the interventions performed during the ERCP shall be recorded and the patient will go through the standard recovery process. Post-procedure after recovery from anesthesia, the patients shall then be evaluated for the presence of pain after ERCP testing on the standard likert pain scale.
If the subject's pain has substantially increased from baseline, subjects shall then be admitted to the hospital and LFTs, a lipase and amylase level shall be drawn and abdominal imaging ordered if needed by the admitting physician (all the standard of care).
Time 1 Days (Visit 2 via phone):
Subjects shall be called 24 hours from ERCP to assess;
- Presence/absence of pain
- If pain, the severity
- Performance of amylase and lipase
- Whether admission, urgent care or emergency department visit did occur
Time 1-30 Days The investigator will await the subjects laboratory values and if > 3 times the upper limit of normal contact the subject via phone.
Time 30 Days (Visit 3 via phone):
Subjects shall be contacted via phone 30 days from ERCP to assess;
- Presence/absence of pain
- If pain, the severity
- Whether admission, urgent care or Emergency Department (ED) visit did occur to a healthcare facility
- Study summary
To detect a difference of 0.24 vs 0.05 a minimum of 48 per group would be needed (using p=0.05).
Descriptive statistics will be used to summarize demographic variables such as age, gender, race, length of stay, as well diagnosis and disease characteristics such as reasons for ERCP, disease intervention, pain,and outcome variables. Data tables will be generated for those variables with means, standard deviation (SD), medians, interquartile range (IQR), and confidence interval (CI). The Chi-Square test will be used to determine the main effect of treatment on ERCP induced pancreatitis. Nonparametric tests will be used to analyze categorical data while normally distributed data will be analyzed using ANOVA to look for treatment effect on other variables of interest.
Binary and Multinomial Logistic Regression will be used to examine predictors of outcome within treatments and across treatments by building interactions into the model (e.g. reasons for ERCP, intervention type). Data analysis will be performed using Systat version 13 and SPSS version 22. A p<0.05 will be considered 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
- 4
| Arm | Type | Receives |
|---|---|---|
| A (NS+Placebo) | Placebo comparator | Drug: Normal Saline, Drug: PlaceboNormal Saline (intravenous during procedure) + Placebo (100mg suppository per rectum prior to procedure ) |
| B (NS+IND) | Active comparator | Drug: Indomethacin, Drug: Normal SalineNormal Saline (intravenous during procedure) + Indomethacin (100mg suppository per rectum prior to procedure ) |
| C (LR+Placebo) | Active comparator | Drug: Lactated Ringer's Solution, Drug: PlaceboLactated ringer's solution (1 Liter, intravenous prior to procedure) + Placebo (100mg suppository per rectum prior to procedure) |
| D (LR+IND) | Experimental | Drug: Indomethacin, Drug: Lactated Ringer's SolutionLactated ringer's solution (1 Liter, intravenous prior to procedure) + Indomethacin (100mg suppository per rectum prior to procedure) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1 Subjects who are undergoing endoscopic retrograde cholangiopancreatography (ERCP)
- Age > 18 years
- Non-pregnant
- Non-prisoners
- Subjects who can sign informed consent
Key exclusion criteria (13 listed)
- Subjects who are not undergoing ERCP
- Age < 18 years
- Pregnancy
- Prisoners
- Subjects lacking the capacity to consent for themselves
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 |
|---|---|---|
| IndomethacinAlso: INDIndomethacin is a non-steroidal anti-inflammatory drug (NSAID) which is commonly used to reduce inflammation caused by gout, osteoarthritis and rheumatoid arthritis. It acts by blocking the cyclo-oxygenase 1 and 2 (COX) receptors. It has also been implicated to prevent post-ERCP pancreatitis | Drug | B (NS+IND), D (LR+IND) |
| Lactated Ringer's SolutionAlso: LRLactated ringer's solution (LR), is an intravenous fluid (IVF) used commonly during endoscopic procedures and operative procedures. It's composition is similar to that of humans including sodium, chloride, potassium, calcium and lactate. Studies have implicated the use of this fluid in pancreatitis treatment and prevention of post-ERCP pancreatitis | Drug | C (LR+Placebo), D (LR+IND) |
| Normal SalineAlso: NSstandard IVF would include 0.9% normal saline (NS) solution used during all endoscopic procedures. 0.9% NS includes equal parts sodium and chloride. | Drug | A (NS+Placebo), B (NS+IND) |
| PlaceboPlacebo would be a suppository 50 mg x 2 | Drug | A (NS+Placebo), C (LR+Placebo) |
Primary outcome
The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Either Elevated Amylase or Lipase 3 x Upper Limit of Normal
Time frame: 30 days after ERCP
amylase or lipase
The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Imaging Suggestive of Acute Pancreatitis
Time frame: 30 days after ERCP
Imaging may include Computer Tomography
18 secondary outcomes
The Number of Participants With Acute Respiratory Distress Syndrome (ARDS) After ERCP as Assessed by ARDSnet Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)
Time frame: 30 days after ERCP
The Number of Participants With Sepsis After ERCP as Assessed by Infectious Source Defined by Positive Microbiology Culture
Time frame: 30 days after ERCP
The Number of Participants With Multiple Organ Failure (MOF) After ERCP as Assessed by Elevated Creatinine Blood Test
Time frame: 30 days after ERCP
The Number of Participants With Multiple Organ Failure (MOF) After ERCP as Assessed by Elevated International Normalized Ratio (INR)
Time frame: 30 days after ERCP
The Number of Participants With Pancreatic Pseudocyst After ERCP as Assessed by Abdominal Imaging Suggestive of Pseudocyst
Time frame: 30 days after ERCP
The Number of Participants With Pancreatic Abscess After ERCP as Assessed by Abdominal Imaging Suggestive of Pancreatic Abscess
Time frame: 30 days after ERCP
The Number of Participants With Perforation After ERCP as Assessed by Abdominal Imaging Suggestive of Perforation
Time frame: 30 days after ERCP
The Number of Participants Who Undergo Surgery After ERCP, as Assessed by Surgical Operative Report
Time frame: 30 days after ERCP
The Number of Participants With Mortality After ERCP as Assessed by Medical Record Reporting
Time frame: 30 days after ERCP
The Number of Participants With Post-procedural Medical Care (ED Visit, Urgent Care, Hospitalization) as Assessed by Medical Record and Patients Self-reporting
Time frame: 30 days after ERCP
The Length of Stay (LOS) of Participants After ERCP if Medical Care is Sought as Assessed in Days
Time frame: 30 days after ERCP
The Number of Participants Who Were Readmitted After ERCP as Assessed by Medical Record and Patients Self-reporting
Time frame: 30 days after ERCP
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2070995Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991 May-Jun;37(3):383-93. doi: 10.1016/s0016-5107(91)70740-2.
- Background: PubMed 22341094ASGE Standards of Practice Committee; Anderson MA, Fisher L, Jain R, Evans JA, Appalaneni V, Ben-Menachem T, Cash BD, Decker GA, Early DS, Fanelli RD, Fisher DA, Fukami N, Hwang JH, Ikenberry SO, Jue TL, Khan KM, Krinsky ML, Malpas PM, Maple JT, Sharaf RN, Shergill AK, Dominitz JA. Complications of ERCP. Gastrointest Endosc. 2012 Mar;75(3):467-73. doi: 10.1016/j.gie.2011.07.010. No abstract available.
- Background: PubMed 12024166Petersen BT. ERCP outcomes: defining the operators, experience, and environments. Gastrointest Endosc. 2002 Jun;55(7):953-8. doi: 10.1067/mge.2002.123622. No abstract available.
- Background: PubMed 23896955Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013 Sep;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218. Epub 2013 Jul 30.
- Background: PubMed 17509029Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR, Spirito F, Pilotto A, Forlano R. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007 Aug;102(8):1781-8. doi: 10.1111/j.1572-0241.2007.01279.x. Epub 2007 May 17.
- Background: PubMed 17703388Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson ML, Williamson PR, Lombard M. Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study. Endoscopy. 2007 Sep;39(9):793-801. doi: 10.1055/s-2007-966723.
- Background: PubMed 19098846Wang P, Li ZS, Liu F, Ren X, Lu NH, Fan ZN, Huang Q, Zhang X, He LP, Sun WS, Zhao Q, Shi RH, Tian ZB, Li YQ, Li W, Zhi FC. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol. 2009 Jan;104(1):31-40. doi: 10.1038/ajg.2008.5.
- Background: PubMed 23164513Ding X, Chen M, Huang S, Zhang S, Zou X. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012 Dec;76(6):1152-9. doi: 10.1016/j.gie.2012.08.021.
- Background: PubMed 22494121Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.
- Background: PubMed 2409946di Sant'Agnese PA, de Mesy Jensen KL, Churukian CJ, Agarwal MM. Human prostatic endocrine-paracrine (APUD) cells. Distributional analysis with a comparison of serotonin and neuron-specific enolase immunoreactivity and silver stains. Arch Pathol Lab Med. 1985 Jul;109(7):607-12.
- Background: PubMed 18375470Elmunzer BJ, Waljee AK, Elta GH, Taylor JR, Fehmi SM, Higgins PD. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut. 2008 Sep;57(9):1262-7. doi: 10.1136/gut.2007.140756. Epub 2008 Mar 28.
- Background: PubMed 12806612Murray B, Carter R, Imrie C, Evans S, O'Suilleabhain C. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology. 2003 Jun;124(7):1786-91. doi: 10.1016/s0016-5085(03)00384-6.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Shaffer RS Mok, MD, MBS principal investigator
The Cooper Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Indomethacin, Lactated Ringer's Solution and Normal Saline in people with Post-ERCP Acute Pancreatitis, run by The Cooper Health System at 1 site in United States.
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 11 inclusion and 13 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: finished, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 27 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With Acute Pancreatitis After ERCP as Assessed by Worsening Abdominal Pain Plus Either Elevated Amylase or Lipase 3 x Upper Limit of Normal (time frame: 30 days after ERCP). The study lists 2 primary outcomes in all. 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 NCT02641561, which also lists 19 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 27 Feb 2018; AzTrials last refreshed its copy on 30 Oct 2026.