Guidewire Management in ERCP

Inadvertent Pancreatic Duct Cannulation as an Independent Predictor of Post- Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Intra-procedural guidewire management is a parameter whose impact remains incompletely understood in terms of its association with post- endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Inadvertent guidewire cannulation of the pancreatic duct (PD) when attempting common bile duct (CBD) cannulation is recognized as a risk factor for PEP. However, to date, no studies have assessed whether a single PD wire cannulation is associated with a higher PEP risk compared to no PD cannulations. Similarly, the relationship between each additional PD cannulation and the incremental magnitude of PEP risk remains unclear. In this study, the investigators will aim to assess whether a single inadvertent PD cannulation (versus no PD cannulation) is associated with an increased risk of PEP (the primary outcome).

Study Overview

• Status: Recruiting
• Conditions: ERCP
• Intervention / Treatment: Other: ERCP with no PD cannulation; Other: ERCP with single PD cannulation

Detailed Description

1. Background and Rationale

   While very effective, endoscopic retrograde cholangiopancreatography (ERCP) is widely known to have the highest adverse event (AE) profile among all commonly performed endoscopic procedures, with a collective AE rate of >10%. Common AEs include post-ERCP pancreatitis (PEP), bleeding, cholangitis, cholecystitis, perforation, and cardiopulmonary events. PEP is the most common, with estimated rates of 5-10%. It is noteworthy that both the incidence of PEP and its associated mortality are rising.

   It is of critical priority to patients, practitioners, and health administrators to investigate factors associated with all AEs and unplanned healthcare encounters (UHEs) following ERCP, especially given that most ERCPs are performed on an outpatient basis. The per-admission costs of post-ERCP UHEs are substantial, exceeding $10,000 and $70,000 for pancreatitis and cholangitis, respectively. PEP alone accounts for an estimated $200+ million in annual healthcare spending in the United States. Thus, researchers must prioritize the study of ERCP outcomes, striving to both identify and modify factors leading to AEs and UHEs.

   Intra-procedural guidewire management is a parameter whose impact remains incompletely understood. Inadvertent guidewire cannulation of the pancreatic duct (PD) when attempting common bile duct (CBD) cannulation is recognized as a risk factor for PEP. However, as inadvertent PD cannulation is highly correlated with difficult CBD cannulation in general, which itself is a risk factor for PEP, these associations are difficult to separate, even in randomized trials. To date, no studies have assessed whether a single PD wire cannulation is associated with a higher PEP risk compared to no PD cannulations. Similarly, the relationship between each additional PD cannulation and the incremental magnitude of PEP risk remains unclear.

2. Research Question and Objectives

   In this study, the investigators will aim to assess whether a single inadvertent PD cannulation (versus no PD cannulation) is associated with an increased risk of PEP (the primary outcome).

3. Methods

Design: Data will be used from the ongoing CReATE project (REB-18-0410). The exposure variable will be a single PD cannulation (versus no PD cannulation) in native papilla cases where the CBD was targeted for any indication. In addition to these variables, other parameters to be assessed include: the presence and timing of pharmacologic PEP prophylaxis, extent and timing of trainee involvement, the number and timing of common bile duct (CBD) cannulation attempts, the depth, timing, trajectory and number of PD cannulation(s), the presence and extent of PD opacification, the size(s) of sphincterotomy and/or sphincteroplasty, intra-procedural pathology, and the composition, caliber and length of any PD or CBD stent(s).

Outcomes: The primary outcome will be PEP, using established definitions. Secondary outcomes (defined a priori) will include PEP severity, overall and specific AEs (bleeding, cholangitis, cardio-pulmonary events), cannulation time and success rate, as well as overall procedure time and success rate.

Sample Size and Power: The investigators estimate 10,700 native papilla cases through the end of 2025. Extrapolating from our existing data (12.3% of eligible patients with a single PD cannulation and 69.4% with no PD cannulation), an estimated 1,316 patients will be exposed and an estimated 7,426 patients be controls. Assuming a two-sided alpha of 0.05, the investigators can demonstrate increases in PEP risk from 5.0% to 7.0% (a relative increase of 40%) with 82.1% power or from 5.0% to 7.5% (a relative increase of 50%) with 93.7% power.

Statistical Analysis: Variables will be compared using Student's t-test for measured variables and chi-squared test for categorical variables. P values < 0.05 will be considered significant. The investigators will use multivariable logistic regression to assess associations between risk factors and having PEP versus not having PEP. Clinically relevant subgroup analyses will also be performed by relevant patient-, endoscopist-, and procedure-related characteristics. Odds ratios per outcome will be reported with 95% CIs.

• Study Type: Observational
• Enrollment (Anticipated): 10700

Contacts and Locations

• Study Contact: Name: Nauzer Forbes, MD MSc; Phone Number: 403 592-5089; Email: nauzer.forbes@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Peter Lougheed Hospital
      • Contact: Nauzer Forbes, MD MSc; Phone Number: 403 592-5089; Email: nauzer.forbes@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients referred to a hospital-based endoscopy unit for ERCP who have a native major papilla.

Description

Inclusion Criteria:

• Subject referred for ERCP, regardless of indication;
• Subject age 18 years or older;
• Subject able to give informed consent to involvement be included.

Exclusion Criteria:

• Previous sphincterotomy or sphincteroplasty
• Subject has a standard contraindication to ERCP;
• Subject or surrogate unable or unwilling to provide informed consent;
• Subject age < 18 years.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No PD cannulation; Patients with native papilla undergoing ERCP for biliary indications with no inadvertent pancreatic duct cannulation	Other: ERCP with no PD cannulation; ERCP with no PD cannulation
Single PD cannulation; Patients with native papilla undergoing ERCP for biliary indications with a single inadvertent pancreatic duct cannulation with a guide wire	Other: ERCP with single PD cannulation; ERCP with single PD cannulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
post-ERCP pancreatitis	Defined using a previously published set of a priori criteria by indication (Cotton et al. Gastrointest Endoscopy 2010; 71:446-54).	30 days

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: McGill University; University of Ottawa; Queen's University; Halton Health (Oakville); Island Health, Victoria, BC
• Investigators: Principal Investigator: Nauzer Forbes, MD MSc, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): February 28, 2026

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 23, 2023
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: REB21-0940

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No