Clinical trial NCT05817721: PROTon Pump Inhibitors and Stent OCclusion Rate Of Lumen Apposing Metal Stents
Official title: PROTon Pump Inhibitors and Stent OCclusion Rate Of Lumen Apposing Metal Stents (PROTOCOL)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Pancreatitis
Keywords: acute pancreatitis
lumen apposing metal stents (LAMS)
proton pump inhibitors (PPI)
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
Collaborators: name: Technical University of Munich
name: Ludwig-Maximilians - University of Munich
name: University Hospital in Halle
name: University of Leipzig
name: University Hospital Heidelberg
name: Landesklinikum Sankt Polten
name: University Hospital, Aachen
name: University of Oldenburg
name: University of Newcastle Upon-Tyne
name: Szeged University
name: University of Pecs
name: Semmelweis University
name: University of Ulm
name: University Hospital Olomouc
name: Brno University Hospital
name: University Hospital Regensburg
name: Klinikum Stadt Hanau
name: University Medicine Greifswald
First posted: 2023-04-18
Enrollment: 893
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Retrospective Cohort Study Primary Outcome Measure Number 1: Association between frequency of LAMS-occlusion and concomitant PPI-intake
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Retrospective Cohort Study Primary Outcome Measure Number 2: Association between frequency of endoscopic necrosectomy and concomitant PPI-intake
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Expert Survey Primary Outcome Measure Number 1: Assessment of the clinical relevance of LAMS-occlusion and LAMS-occlusion-related complications
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Expert Survey Primary Outcome Measure Number 2: Assessment of the clinical management of LAMS-occlusion in the respective participating centers
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
Secondary outcomes:
measure: Retrospective Cohort Study Secondary Outcome Number 1: Strength of association between PPI intake and the incidence of GI bleeding rates.
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Retrospective Cohort Study Secondary Outcome Number 2: Strength of association between PPI intake and incidence of WON progression on cross sectional imaging.
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Retrospective Cohort Study Secondary Outcome Number 3: Strength of association between PPI intake and incidence of superinfection of the WON
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Retrospective Cohort Study Secondary Outcome Number 4: Strength of association between PPI intake and incidence of sepsis events.
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Retrospective Cohort Study Secondary Outcome Number 5: Strength of association between PPI intake and length of hospital stay (days).
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: 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.
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: Expert Survey Secondary Outcome Number 2: To assess whether the respective clinical center has a SOP regarding LAMS and concomitant PPI-intake.
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
measure: 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".
timeFrame: Until LAMS-removal, an average of 4 weeks after implantation
Other outcomes:
Locations:
city: Goettigen
country: Germany
facility: University Medical Center Goettingen
state: Lower saxony
Study officials:
affiliation: Department of Gastroenterology, University Hopsital Goettingen
name: Jacob Hamm
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology, University Hopsital Goettingen
name: Christoph Ammer-Herrmenau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology, University Hopsital Goettingen
name: Volker Ellenrieder, Professor
role: STUDY_CHAIR
References:
citation: Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.
citation: Werge M, Novovic S, Schmidt PN, Gluud LL. Infection increases mortality in necrotizing pancreatitis: A systematic review and meta-analysis. Pancreatology. 2016 Sep-Oct;16(5):698-707. doi: 10.1016/j.pan.2016.07.004. Epub 2016 Jul 9.
citation: Yasuda I, Takahashi K. Endoscopic management of walled-off pancreatic necrosis. Dig Endosc. 2021 Mar;33(3):335-341. doi: 10.1111/den.13699. Epub 2020 Jun 7.
citation: Chandrasekhara V, Barthet M, Deviere J, Bazerbachi F, Lakhtakia S, Easler JJ, Peetermans JA, McMullen E, Gjata O, Gourlay ML, Abu Dayyeh BK. Safety and efficacy of lumen-apposing metal stents versus plastic stents to treat walled-off pancreatic necrosis: systematic review and meta-analysis. Endosc Int Open. 2020 Nov;8(11):E1639-E1653. doi: 10.1055/a-1243-0092. Epub 2020 Oct 22.
citation: Scarpignato C, Gatta L, Zullo A, Blandizzi C; SIF-AIGO-FIMMG Group; Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016 Nov 9;14(1):179. doi: 10.1186/s12916-016-0718-z.
citation: Lorenz P, Lynen Jansen P, Beyer G, Hoffmeister A, Lerch MM, Mayerle J. S3-Leitlinie Pankreatitis - Leitlinienreport der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) - September 2021 - AWMF Registernummer 021-003. Z Gastroenterol. 2022 Mar;60(3):e236-e247. doi: 10.1055/a-1713-4244. Epub 2022 Mar 9. No abstract available. German.
citation: Murata A, Ohtani M, Muramatsu K, Matsuda S. Effects of proton pump inhibitor on outcomes of patients with severe acute pancreatitis based on a national administrative database. Pancreatology. 2015 Sep-Oct;15(5):491-496. doi: 10.1016/j.pan.2015.07.006. Epub 2015 Aug 8.
citation: Yoo JH, Kwon CI, Yoo KH, Yoon H, Kim WH, Ko KH, Hong SP, Park PW. [Effect of proton pump inhibitor in patients with acute pancreatitis - pilot study]. Korean J Gastroenterol. 2012 Dec;60(6):362-7. doi: 10.4166/kjg.2012.60.6.362. Korean.
citation: Powers PC, Siddiqui A, Sharaiha RZ, Yang G, Dawod E, Novikov AA, Javia A, Edirisuriya C, Noor A, Mumtaz T, Iqbal U, Loren DE, Kowalski TE, Cosgrove N, Alicea Y, Tyberg A, Andalib I, Kahaleh M, Adler DG. Discontinuation of proton pump inhibitor use reduces the number of endoscopic procedures required for resolution of walled-off pancreatic necrosis. Endosc Ultrasound. 2019 May-Jun;8(3):194-198. doi: 10.4103/eus.eus_59_18.
citation: Martins de Oliveira R, Antunes E, Pedrazzoli J Jr, Gambero A. The inhibitory effects of H+ K+ ATPase inhibitors on human neutrophils in vitro: restoration by a K+ ionophore. Inflamm Res. 2007 Mar;56(3):105-11. doi: 10.1007/s00011-006-6127-6.
citation: Handa O, Yoshida N, Fujita N, Tanaka Y, Ueda M, Takagi T, Kokura S, Naito Y, Okanoue T, Yoshikawa T. Molecular mechanisms involved in anti-inflammatory effects of proton pump inhibitors. Inflamm Res. 2006 Nov;55(11):476-80. doi: 10.1007/s00011-006-6056-4.
citation: Hackert T, Tudor S, Felix K, Dovshanskiy D, Hartwig W, Simon WA, Werner J. Effects of pantoprazole in experimental acute pancreatitis. Life Sci. 2010 Oct 23;87(17-18):551-7. doi: 10.1016/j.lfs.2010.09.008. Epub 2010 Sep 17.