PROTon Pump Inhibitors and Stent OCclusion Rate Of Lumen Apposing Metal Stents (PROTOCOL)

June 13, 2025 updated by: Christoph Ammer-Herrmenau, University Medical Center Goettingen

PROTon Pump Inhibitors and Stent OCclusion Rate Of Lumen Apposing Metal Stents (PROTOCOL)

The goal of this observational retrospective cohort study in combination with an expert study is to assess the clinical relevance and management of Lumen apposing metal stent (LAMS)-occlusion and LAMS-occlusion-related complications as well as the influence of proton pump inhibitors (PPI) on LAMS-occlusion.

The main questions this study aims to answer are:

  • the individual management of LAMS-occlusion and LAMS-occlusion-related complications in the respective centers participating in the study.
  • if there is an association between PPI-intake and LAMS-occlusion and endoscopic necrosectomies.

Participants for the retrospective cohort study will be enrolled retrospectively among European centers with expertise in pancreatology. The expert survey will be distributed European-wide to centers with special expertise in pancreatology.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A common complication of acute pancreatitis is the formation of necrosis in 5-10% of all patients, which leads to an increased overall mortality of 28% for infected necroses. Currently, lumen apposing metal stents (LAMS) are widely used to address necrotic masses. LAMS-occlusion is postulated to be a considerable complication. However, the prevalence, clinical impact and management of LAMS-occlusion-related complications remains uncertain. Moreover, the German guidelines for management of acute pancreatitis do not specify whether a concomitant proton pump inhibitor (PPI)-therapy should be discontinued or not. A recent study suggested a lower rate of LAMS-occlusions, but a higher number of required endoscopic necrosectomies upon concomitant PPI-therapy. Thus, current data are conflicting.

The investigators therefore aim to perform an expert survey and a retrospective cohort study to elucidate the clinical importance of LAMS-occlusion-related complications and the effect of PPI-intake on occlusion. First, a survey will be sent to European centers with special expertise in pancreatology. Here, the investigators aim to assess the number of LAMS applied annually, whether the experts consider occlusion a clinically relevant complication, and whether there are standard operating procedures for LAMS-occlusion and PPI-discontinuation. Second, the investigators will perform a retrospective multicenter cohort study to assess patient data for PPI intake, frequency of LAMS-occlusion and other complications using a RedCap database.

Quality assurance and data checks of the data entered will be performed by the study coordinator after the initial data entry of the participating centers. For missing data, for which the RedCap form cannot be filled out, the online forms comprise extra fields for "missing data". The data entered in the RedCap online survey will stem from paper or electronic case report forms depending which of these are used at the respective centers. Source data verification will be performed by the participating centers themselves upon data entry into the online questionnaires.

A standard operating procedure will be handed out to the participating centers which will feature any information about how data should be entered. Here, the minimum number of patients which needs to be entered into the study in order to participate will be addressed. The maximum of patients who can be entered is dependent on the respective centers; in principle all patients who received a LAMS for drainage of a WON in the respective centers can be included. As the investigators perform a retrospective study, there will be no need to account for reporting of adverse events.

Based on a power calculation of a preliminary in-house dataset from the University Hospital Goettingen the investigators aim to include a total number of 639 patients.

For missing, unavailable, non-reported or uninterpretable data, the RedCap survey will comprise extra fields as described above. In these, the participating researcher can state that data is missing. If this information is essential for the primary or secondary endpoints of our study, the data entry can be excluded from further analyses by the data monitoring committee.

For the statistical analyses of the data gathered from the expert survey the investigators will apply a Fisher/Chi2-test to assess the clinical relevance as well as the clinical management of LAMS-occlusion and LAMS-occlusion-related complications. For the retrospective cohort study, a Chi2-test will be used to address correlations between PPI-intake and LAMS-occlusion. To assess the frequency of occlusion-related-complications, risk factors for LAMS-occlusion beyond PPI-intake and differences in clinical management of LAMS-occlusion in the respective centers, logistic regression/LASSO will be applied.

Study Type

Observational

Enrollment (Actual)

893

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Lower saxony
      • Goettigen, Lower saxony, Germany, 37075
        • University Medical Center Goettingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

All patients included in the retrospective cohort study will be from private/public non-academic or academic teaching hospitals in Europe.

All patients above 18 years of age who received a lumen apposing metal stent (LAMS) for drainage of a walled off necrosis (WON) upon acute pancreatitis will be included.

Moreover, the expert survey will be distributed to European experts (gastroenterological interventionalists) from private/public non-academic or academic teaching hospitals with special expertise in pancreatology.

Description

Retrospective cohort study:

Inclusion Criteria:

- Patients in which a Lumen apposing metal stent (LAMS) was applied into a walled off necrosis (WON) as a complication of an acute pancreatitis (AP).

Exclusion Criteria:

  • Patients in which a LAMS was applied into a pseudocyst instead of a WON.
  • Patients in which a LAMS was used to address a postoperative pancreatic fistula (POPF).
  • Patients in which concomitant PPI-treatment was not assessed/not documented.

Expert survey:

Inclusion Criteria:

- European experts (gastroenterological interventionalists) with expertise in pancreatology

Exclusion Criteria:

  • Centers which apply less than 10 LAMS per year
  • Centers with less than two years experience with LAMS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PPI-group
Patients who received a lumen apposing metal stent (LAMS) for drainage of a walled off necroses (WON) upon acute pancreatitis (AP) and were prescribed proton pump inhibitors (PPI) concomitantly
Drug: Proton pump inhibitor
Patients who received a lumen apposing metal stent (LAMS) for drainage of a walled off necrosis (WON) upon acute pancreatitis will be divided into a PPI/Non-PPI group depending on if they concomitantly were prescribed a PPI or not
Device: LAMS-implantation
Patients who received a lumen apposing metal stent (LAMS) for drainage of a walled off necrosis (WON) upon acute pancreatitis
Non-PPI-group
Patients who received a lumen apposing metal stent (LAMS) for drainage of a walled off necroses (WON) upon acute pancreatitis (AP) and were not prescribed proton pump inhibitors (PPI) concomitantly
Device: LAMS-implantation
Patients who received a lumen apposing metal stent (LAMS) for drainage of a walled off necrosis (WON) upon acute pancreatitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expert Survey Primary Outcome Measure Number 1: Assessment of the clinical relevance of LAMS-occlusion and LAMS-occlusion-related complications
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The expert will be asked if he had experiences with complications after total/partial LAMS-occlusion (yes/no). Moreover, the expert will be asked if he would consider these as frequent complications (yes/no). Next, the expert will be asked how frequent he would consider complications after total/partial LAMS-occlusion to occur (scale 0-20%). Finally, the expert will be asked which complications he had witnessed after total/partial LAMS-occlusion (progression of the pancreatic collection, infection of the WON, sepsis, other).
Until LAMS-removal, an average of 4 weeks after implantation
Expert Survey Primary Outcome Measure Number 2: Assessment of the clinical management of LAMS-occlusion in the respective participating centers
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
Two clinical cases will be presented. The first case will be suggestive for a total LAMS occlusion with infection/sepsis as a complication consecutive to the stent-occlusion. The second case will be suggestive for a partial LAMS occlusion with no apparent complication. For each case, the expert will be asked if he would consider this a complication (yes/no). Moreover, it will be asked if the expert would remove the LAMS (yes/no), if he would place pigtails over the ostium afterwards (yes/no) and if not what he would do otherwise (endoscopic necrosectomy, place pigtail through the LAMS, disrupted pancreatic duct evaluation via endoscopic retrograde cholangiopancreatography/magnet resonance cholangiopancreatography (ERCP/MRCP), endoscopic papillotomy, other).
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Primary Outcome Measure Number 1: Association between frequency of LAMS-occlusion and concomitant PPI-intake
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
All patients who received a LAMS from the time-point since LAMS have been used at the respective centers will be included. In all patients who received LAMS, their medical records will be checked if a PPI was taken or not. Next, it will be assessed how many patients who took PPIs (PPI-group) had a LAMS-occlusion in comparison with the patients who did not take a PPI (Non-PPI-group). To associate the PPI intake/no PPI intake with LAMS occlusion, we will fit a multiple logistic mixed-effects model including factors potentially affecting the LAMS occlusion rate. As random effects we will include the record identification number and the years of LAMS placement as a surrogate for experience with LAMS.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Primary Outcome Measure Number 2: Association between frequency of endoscopic necrosectomy and concomitant PPI-intake
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
All patients who received a LAMS from the time-point since LAMS have been used at the respective centers will be included. In all patients who received LAMS, their medical records will be checked if a PPI was taken or not. Next, it will be assessed how many necrosectomy sessions were performed in patients who took PPIs (PPI-group) in comparison with the patients who did not take a PPI (Non-PPI-group). To associate the PPI intake/no PPI intake with the number of endoscopic necrosectomy sessions, we will perform a multiple negative binomial mixed-effects model taking into account counfounders such as the year in which a LAMS was placed.
Until LAMS-removal, an average of 4 weeks after implantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expert Survey Secondary Outcome Number 1: To assess if a standard operating procedure (SOP) for follow-up-examinations regarding stent occlusion after LAMS-implantation exists in the respective centers.
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The expert will basked if a SOP for apparative follow-up-examinations after LAMS application exists at their center (yes/no/unknown). Moreover, it will be asked how many follow up examinations are performed (1, 2, 3 or more), at which time-points (<3 days, within 1 week, 2,3,4,5-8 weeks) and how (CT, MRI, gastroscopy, endoscopic ultrasound, abdominal ultrasound) these are performed. Additionally, it will be asked when the LAMS would be removed normally (≤4weeks, 5-8 weeks, ≥9 weeks after implantation). Moreover, it will be asked which procedure is normally followed after LAMS removal (change LAMS to pigtails, just remove the LAMS, other).
Until LAMS-removal, an average of 4 weeks after implantation
Expert Survey Secondary Outcome Number 2: To assess whether the respective clinical center has a SOP regarding LAMS and concomitant PPI-intake.
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The expert will be asked, if proton pump inhibitors are continued/discontinued upon LAMS-application at his/her center (should be discontinued, should be continued with the same dosage, should be continued with another dosage, currently no standard procedure). If the PPI should be continued in another dosage, it will be asked whether it should be continued in half the standard dose, standard dose, double standard dose or more than standard dose. Moreover, it will be asked if any specific PPI should be discontinued and if yes which of the following (Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole, Rabeprazole).
Until LAMS-removal, an average of 4 weeks after implantation
Expert Survey Secondary Outcome Number 3: To assess the experts definition of the term "LAMS-occlusion" in general, as well as the term "partial LAMS occlusion".
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The expert will be asked which of the following potential causes of LAMS occlusion he/she would include in a universal valid definition for reasons of LAMS-occlusion: tissue ingrowth, tissue overgrowth, food impaction, impaction with liquid necrotic debris, impaction with solid necrotic debris, blood clot formation, stent migration, stent kinking, stent compression, stent fracture, other. Moreover, the expert will be asked how he/she would define partial LAMS-occlusion: An occlusion which is still passable with the endoscope; An occlusion in which you can still see through the LAMS with the optics of the endoscope; An occlusion with liquid parts, other.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Secondary Outcome Number 1: Strength of association between PPI intake and the incidence of GI bleeding rates.
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The first secondary aim of this study is to assess the strength of an association between PPI intake and the incidence of GI bleeding rates by performing logistic regression with Firth's correction.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Secondary Outcome Number 2: Strength of association between PPI intake and incidence of WON progression on cross sectional imaging.
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The second secondary aim of this study is to assess the strength of an association between PPI intake and the incidence of WON progression on cross sectional imaging by performing logistic regression with Firth's correction.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Secondary Outcome Number 3: Strength of association between PPI intake and incidence of superinfection of the WON
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The third secondary aim of this study is to assess the strength of an association between PPI intake and the incidence of superinfection of the WON by performing logistic regression with Firth's correction.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Secondary Outcome Number 4: Strength of association between PPI intake and incidence of sepsis events.
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The fourth secondary aim of this study is to assess the strength of an association between PPI intake the incidence of sepsis events by performing logistic regression with Firth's correction.
Until LAMS-removal, an average of 4 weeks after implantation
Retrospective Cohort Study Secondary Outcome Number 5: Strength of association between PPI intake and length of hospital stay (days).
Time Frame: Until LAMS-removal, an average of 4 weeks after implantation
The fifth secondary aim of this study is to assess the strength of an association between PPI intake and the length of hospital stay (days) by performing logistic regression with Firth's correction.
Until LAMS-removal, an average of 4 weeks after implantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Goettingen

Collaborators

University of Pecs
Ludwig-Maximilians - University of Munich
University of Leipzig
University Medicine Greifswald
University Hospital Heidelberg
Technical University of Munich
University of Ulm
Brno University Hospital
University Hospital Olomouc
University of Newcastle Upon-Tyne
Semmelweis University
Szeged University
University Hospital Regensburg
University Hospital, Aachen
Landesklinikum Sankt Polten
University of Oldenburg
Klinikum Stadt Hanau
University Hospital in Halle

Investigators

  • Principal Investigator: Jacob Hamm, Department of Gastroenterology, University Hopsital Goettingen
  • Principal Investigator: Christoph Ammer-Herrmenau, MD, Department of Gastroenterology, University Hopsital Goettingen
  • Study Chair: Volker Ellenrieder, Professor, Department of Gastroenterology, University Hopsital Goettingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2023

Primary Completion (Actual)

March 29, 2024

Study Completion (Actual)

March 29, 2024

Study Registration Dates

First Submitted

March 30, 2023

First Submitted That Met QC Criteria

April 16, 2023

First Posted (Actual)

April 18, 2023

Study Record Updates

Last Update Posted (Actual)

June 15, 2025

Last Update Submitted That Met QC Criteria

June 13, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-02441

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Collaborators of this study that recruited patients in the PROTOCOL trial may claim access to the final dataset to perform post-hoc studies; these proposals will be reviewed and granted by the steering committee.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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