Clinical trial NCT04492137: Prospective Comparison Between Ultra Early NKF Versus Standard Cannulation Alone
Official title: Prospective Comparison Between Ultra Early NKF Versus Standard Cannulation Alone in a Group of High and Low Risk of Pep, Submitted to Pep Prophylaxis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreatitis
Keywords: ERCP
Biliary cannulation
Needle-knife fistulotomy
Standard cannulation methods
Lead sponsor: University of Minho
Sponsor class: OTHER
Collaborators: name: Unidade Local de Saúde do Alto Minho
First posted: 2020-07-30
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: We will conduct a prospective randomized study. Participants will be randomized by computer into two groups at a 1:1 ratio

1. participants submitted to ultra early NKF
2. participants submitted to standard cannulation techniques (including double-guidewire-assisted cannulation)
Primary purpose: OTHER

Brief summary: Compare the ultra early fistulotomy strategy with standard cannulation methods for accessing the bile duct during endoscopic retrograde cholangiopancreatography (ERCP)

Detailed description: 1. Introduction

   Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced procedure which is widely used in the diagnosis and treatment of a variety of benign and malignant pancreatobiliary disorders1,2,3,4,5.

   Selective cannulation of the common bile duct (CBD) is the most important and challenging step in a biliary endoscopic retrograde cholangiopancreatography6,7. However, in the first ERCP, even in experienced hands, biliary cannulation may fail in up to 15 % - 35 % of cases when using standard methods alone8. In this subset of patients, additional cannulation techniques are needed to access the CBD in order to continue with the ERCP.

   Precut is the most common strategy used by experienced endoscopists, when conventional methods have failed7. Needle knife fistulotomy (NKF) and conventional precut are the two most common variants. Recently published guidelines recommend opting for NKF, as evidence suggests a lower risk of adverse events, especially pancreatitis, when used early in the biliary cannulation algorithm7,9.

   Technically NKF is the creation of an artificial fistula between the most protuberant portion of the papilla, which represents the intraduodenal portion of the CBD and the biliary tract by using a diathermic cutter of the needle type6,10,11,12,13,14,15,16,17,18. Its big advantage over conventional precut is that it avoids the contact of the cutting device with the papillary orifice and therefore avoiding direct thermal injury to the pancreatic duct.

   Although NKF was originally developed as a rescue technique, to be used after previous failed standard cannulations attempts, it is being increasingly used at an early stage during ERCP. Given its safety and feasibility some authors even advocate, the once unreasonable, primary use without previous standard cannulation attempts10,11,19,20.
2. Financial resources

   All participants included in this study will perform ERCP, laboratory tests and other complementary diagnostic tests after a duly justified medical prescription. Therefore there are no additional costs or consumption of hospital resources.
3. Ethical considerations In this study, participants will be included after informed consent. Anonymity and confidentiality will be safeguarded by assigning an individual numeric code. It will also be explained the possibility of withdrawing from the study at any time, with the guarantee of the total elimination of data. All researchers involved in the study will adhere to the Rules of Ethical Conduct and Best Practices in order to comply with the precepts of the Declaration of Helsinki, the Convention on Human Rights and Biomedicine, the guidelines of the Council for International Organizations of Medical Sciences and the Guide to Good Clinical Practice.
4. Statistical analysis

   Qualitative variables will be summarized using absolute and relative frequencies, and quantitative variables will be summarized using the mean and standard deviation or the median and interquartile range, depending on their distribution profiles. The normality of the quantitative variables will be assessed using the histogram distribution.

   A sample of 334 (167 in each group) patients will provide 80% power to detect a difference of 5% in pancreatitis rates between the two groups based on a chi-square test, assuming a pancreatitis rate of 1% among primary fistulotomy, 6 and a one-tailed alpha of 0.05.

   Relations between categorical variables will be assessed using a chi-square test and Fisher´s exact test. Differences between two or more groups of independent non-normally distributed quantitative variables will be evaluated using a Kruskal-Wallis test.

   To explain the risk of pancreatitis, a binomial logistic regression model with multiple predictors will be performed.

   The null hypothesis will be rejected when the test statistics p-values are less than \<0.05. Statistical analysis, sample size calculation and graphics will be performed using Stata software (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, StataCorp LP)
5. Expected results

The results of this study will contribute to a better understanding of what is the best algorithm to follow when performing an ERCP.

Eligibility criteria: From June 1, 2020 to June 1, 2022, all individuals referred for ERCP in the Digestive Endoscopy Unit of Santa Luzia Hospital (Unidade Local de Saúde do Alto Minho) will be invited to participate in the study.

Inclusion Criteria:

* ERCP with indication for biliary access
* Naïve papilla

Exclusion Criteria:

* Flat papillas
* Intradiverticular / Diverticular border papillas
* Patients unable to sign or understand the informed consent
* Patients with surgically altered anatomy
* Patients with tumors of the papilla
* Previous sphincterotomy
* Spontaneous papillary fistula
* Papilla not visualized

Primary outcomes:
measure: Adverse events
timeFrame: 30 days from the procedure
measure: Technical success
timeFrame: 1 day (same day of the procedure)
Secondary outcomes:
measure: Adverse event rate among sub groups
timeFrame: 30 days from the procedure
measure: Technical success among sub groups
timeFrame: 1 day (same day of the procedure)
Other outcomes:
Locations:
city: Viana do Castelo
country: Portugal
facility: Santa Luzia Hospital, ULS Alto Minho
Study officials:
References:
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