Lactated Ringers With or Without Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

NCT02641561 | Completed Phase 3 Results DMC

• 1 other identifier: 14-091
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief 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. It is our hope to evaluate the combination of these two modalities for preventing post-ERCP pancreatitis compared with either modality alone.

Conditions

Post-ERCP Acute Pancreatitis

Keywords

Pancreatitis; ERCP; Indomethacin; Lactated ringer's

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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)

  30 days after ERCP

• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)

  30 days after ERCP

• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)

  30 days after ERCP

• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)

  30 days after ERCP

• The Number of Participants With Systemic Inflammatory Response Syndrome (SIRS) After ERCP as Assessed by the SIRS Criterion (Below)

  30 days after ERCP

Study Arms (4)

A (NS+Placebo)

PLACEBO COMPARATOR

Normal Saline (intravenous during procedure) + Placebo (100mg suppository per rectum prior to procedure )

Drug: Normal Saline; Drug: Placebo

B (NS+IND)

ACTIVE COMPARATOR

Normal Saline (intravenous during procedure) + Indomethacin (100mg suppository per rectum prior to procedure )

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)

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)

Drug: Indomethacin; Drug: Lactated Ringer's Solution

Interventions

Indomethacin DRUG

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

Also known as: IND

B (NS+IND); D (LR+IND)

Lactated Ringer's Solution DRUG

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

Also known as: LR

C (LR+Placebo); D (LR+IND)

Normal Saline DRUG

standard IVF would include 0.9% normal saline (NS) solution used during all endoscopic procedures. 0.9% NS includes equal parts sodium and chloride.

Also known as: NS

A (NS+Placebo); B (NS+IND)

Placebo DRUG

Placebo would be a suppository 50 mg x 2

A (NS+Placebo); C (LR+Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• The Cooper Health System: lead

Study Sites (1)

Cooper Hospital

Camden, New Jersey, 08103, United States

Location

Related Publications (19)

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  PMID: 22341094 BACKGROUND

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  PMID: 12024166 BACKGROUND

• Tenner 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.

  PMID: 23896955 BACKGROUND

• Andriulli 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.

  PMID: 17509029 BACKGROUND

• Williams 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.

  PMID: 17703388 BACKGROUND

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  PMID: 19098846 BACKGROUND

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  PMID: 23164513 BACKGROUND

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  PMID: 22494121 BACKGROUND

• di 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.

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• Elmunzer 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.

  PMID: 18375470 BACKGROUND

• Murray 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.

  PMID: 12806612 BACKGROUND

• Rome Foundation. Guidelines--Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders. J Gastrointestin Liver Dis. 2006 Sep;15(3):307-12. No abstract available.

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• Prajapati 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.

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• Sherman 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.

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  PMID: 17383459 BACKGROUND

• Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011 Aug;9(8):710-717.e1. doi: 10.1016/j.cgh.2011.04.026. Epub 2011 May 12.

  PMID: 21645639 BACKGROUND

• Buxbaum J, Yan A, Yeh K, Lane C, Nguyen N, Laine L. Aggressive hydration with lactated Ringer's solution reduces pancreatitis after endoscopic retrograde cholangiopancreatography. Clin Gastroenterol Hepatol. 2014 Feb;12(2):303-7.e1. doi: 10.1016/j.cgh.2013.07.026. Epub 2013 Aug 3.

  PMID: 23920031 BACKGROUND

• Mok SRS, Ho HC, Shah P, Patel M, Gaughan JP, Elfant AB. Lactated Ringer's solution in combination with rectal indomethacin for prevention of post-ERCP pancreatitis and readmission: a prospective randomized, double-blinded, placebo-controlled trial. Gastrointest Endosc. 2017 May;85(5):1005-1013. doi: 10.1016/j.gie.2016.10.033. Epub 2016 Nov 2.

  PMID: 27816497 DERIVED

MeSH Terms

Conditions

Pancreatitis

Interventions

Indomethacin; Ringer's Lactate; Saline Solution

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

We did not power this study to detect a difference between our other comparative groups (NS+IND, LR+placebo), these comparisons may have been prone to type II statistical errors. Single center experience is another possible limitation.

Results Point of Contact

• Title: Shaffer R. S. Mok, M.D., M.B.S.
• Organization: Cooper University Hospital

mok.shaffer@gmail.com

6099804564

Study Officials

• Shaffer RS Mok, MD, MBS

  The Cooper Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Instructor

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: December 29, 2015
• Study Start: October 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: February 27, 2018
• Results First Posted: February 27, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)