Biliary Candidiasis - Optimization of Diagnostics and Therapy

NCT ID: NCT01109550

Last Updated: 2022-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

123 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-04-30

Study Completion Date

2013-11-30

Brief Summary

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Biliary obstruction and cholangitis are common problems in gastroenterology and need specific therapeutic interventions. Besides a variety of potential causes, infections of the biliary tract with Candida and other fungal species have increasingly been reported in the last few years. Especially interesting is the question, if patients with positive fungal cultures of bile samples should be treated or not and under which circumstances. The primary aim of the present study is to evaluate wether positive fungal cultures of bile samples indicate fungal infection of the biliary tract, rather colonization or simply contamination during endoscopic retrograde cholangiopancreatography (ERCP) procedure.

Detailed Description

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Background:

Biliary obstruction and cholangitis are common problems in gastroenterology and need specific therapeutic interventions. Besides a variety of potential causes, infections of the biliary tract with Candida and other fungal species have increasingly been reported in the last few years \[1-6\]. Fungal infections can even lead to common bile duct (CBD) obstruction, as previously reported \[7\]. Because of the difficulty of gaining bile samples, little is known about the microbial flora of the bile. In a first prospective, observational study, 123 consecutive patients undergoing ERCP for various indications were screened for fungal species \[8\]. According to this data Candida species may be very frequently be detected in the bile (54/123 patients, 44 % of the cases). As significant risk factors immunosuppression and long-term antibiotic therapy were identified. The main issue in this context is whether positive diagnostic findings represent fungal infection or fungal colonization. Especially interesting is the question, if patients with positive fungal cultures of bile samples should be treated or not and under which circumstances.

Study Aim:

The primary aim of the present study is to evaluate wether positive fungal cultures of bile samples indicate fungal infection of the biliary tract, rather colonization or simply contamination during ERCP procedure. In addition to mycological analysis of bile samples, tissue samples of the common bile duct are collected to confirm fungal invasion.

Study design:

The study is designed as a single-center, non-randomized, observational study. The conducting center is the University Hospital of Muenster, Department of Medicine B, Gastroenterology. The examinations are performed by two experienced gastroenterologists (D. D., H. U.).

Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure:

ERCP is performed using a conventional duodenoscope as described in the literature. To exclude contamination artefacts, smears of the endoscope working channel (elevator) will be taken before and after the examination. Furthermore buccal smears and stool samples will be taken to get an impression of the individual transient flora. Endoscopic transpapillary bile duct biopsy for diagnosing an invasive fungal infection will be performed. Transpapillary biopsies as confirmed by the present literature cause no increased risk for post-interventional bleeding and infection \[9-12\]. Additionally with routinely taken blood samples (hemoglobin and lipase), candida-antigen-serology and blood-cultures will be gained.

Ethics:

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was a priori approved by the local ethics committee of the University of Muenster.

Statistical methods:

The data will be analyzed using standard statistical methods. As observational study, no power-analysis will reasonable - nevertheless data will be shown with confidence interval. All statistical analyses will be performed in cooperation with the Department of Medical Informatics and Biomathematics.

Conditions

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Secondary Cholangitis Bile Duct Strictures of Unknown Origin

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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with biliary candidiasis

Patients with positive fungal cultures of bile samples.

ERCP

Intervention Type PROCEDURE

endoscopic retrograde cholangiopancreatography transpapillary biopsies

without biliary candidiasis

Patients with negative fungal cultures of bile samples.

ERCP

Intervention Type PROCEDURE

endoscopic retrograde cholangiopancreatography transpapillary biopsies

Interventions

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ERCP

endoscopic retrograde cholangiopancreatography transpapillary biopsies

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Secondary cholangitis
* Bile duct strictures of unknown origin
* Age ≥ 18 years
* All individuals provide written informed consent before entering the trial

Exclusion Criteria

* Ineffective aspiration of bile samples
* Pregnant or breastfeeding patient
* Age \< 18 years
* Missing informed consent
* Missing cooperation (language barrier, amblyacousia, psychiatric disease)
* Refusal of participation
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

University Hospital Muenster

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philipp Lenz, M.D.

Role: STUDY_CHAIR

University Hospital of Muenster

Dirk Domagk, M.D.

Role: STUDY_CHAIR

University Hospital of Muenster

Locations

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Unitersity Hospital of Muenster, Department of Medicine B

Münster, , Germany

Site Status

Countries

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Germany

References

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Banerjee SN, Emori TG, Culver DH, Gaynes RP, Jarvis WR, Horan T, Edwards JR, Tolson J, Henderson T, Martone WJ. Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System. Am J Med. 1991 Sep 16;91(3B):86S-89S. doi: 10.1016/0002-9343(91)90349-3.

Reference Type BACKGROUND
PMID: 1928197 (View on PubMed)

Bouche H, Housset C, Dumont JL, Carnot F, Menu Y, Aveline B, Belghiti J, Boboc B, Erlinger S, Berthelot P, et al. AIDS-related cholangitis: diagnostic features and course in 15 patients. J Hepatol. 1993 Jan;17(1):34-9. doi: 10.1016/s0168-8278(05)80518-5.

Reference Type BACKGROUND
PMID: 8445217 (View on PubMed)

Domagk D, Fegeler W, Conrad B, Menzel J, Domschke W, Kucharzik T. Biliary tract candidiasis: diagnostic and therapeutic approaches in a case series. Am J Gastroenterol. 2006 Nov;101(11):2530-6. doi: 10.1111/j.1572-0241.2006.00663.x. Epub 2006 Oct 4.

Reference Type BACKGROUND
PMID: 17029620 (View on PubMed)

George J, Baillie J. Contemporary Management of Biliary Tract Infections. Curr Infect Dis Rep. 2005 Mar;7(2):108-114. doi: 10.1007/s11908-005-0069-y.

Reference Type BACKGROUND
PMID: 15727737 (View on PubMed)

Singh N, Wagener MM, Marino IR, Gayowski T. Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices. Transplantation. 2002 Jan 15;73(1):63-7. doi: 10.1097/00007890-200201150-00011.

Reference Type BACKGROUND
PMID: 11792979 (View on PubMed)

Wig JD, Singh K, Chawla YK, Vaiphei K. Cholangitis due to candidiasis of the extra-hepatic biliary tract. HPB Surg. 1998;11(1):51-4. doi: 10.1155/1998/75730.

Reference Type BACKGROUND
PMID: 9830582 (View on PubMed)

Domagk D, Bisping G, Poremba C, Fegeler W, Domschke W, Menzel J. Common bile duct obstruction due to candidiasis. Scand J Gastroenterol. 2001 Apr;36(4):444-6. doi: 10.1080/003655201300051397.

Reference Type BACKGROUND
PMID: 11336173 (View on PubMed)

Lenz P, Conrad B, Kucharzik T, Hilker E, Fegeler W, Ullerich H, Heinecke A, Domschke W, Domagk D. Prevalence, associations, and trends of biliary-tract candidiasis: a prospective observational study. Gastrointest Endosc. 2009 Sep;70(3):480-7. doi: 10.1016/j.gie.2009.01.038. Epub 2009 Jun 24.

Reference Type BACKGROUND
PMID: 19555935 (View on PubMed)

Domagk D, Poremba C, Dietl KH, Senninger N, Heinecke A, Domschke W, Menzel J. Endoscopic transpapillary biopsies and intraductal ultrasonography in the diagnostics of bile duct strictures: a prospective study. Gut. 2002 Aug;51(2):240-4. doi: 10.1136/gut.51.2.240.

Reference Type BACKGROUND
PMID: 12117887 (View on PubMed)

Kubota Y, Takaoka M, Tani K, Ogura M, Kin H, Fujimura K, Mizuno T, Inoue K. Endoscopic transpapillary biopsy for diagnosis of patients with pancreaticobiliary ductal strictures. Am J Gastroenterol. 1993 Oct;88(10):1700-4.

Reference Type BACKGROUND
PMID: 8213710 (View on PubMed)

Sugiyama M, Atomi Y, Wada N, Kuroda A, Muto T. Endoscopic transpapillary bile duct biopsy without sphincterotomy for diagnosing biliary strictures: a prospective comparative study with bile and brush cytology. Am J Gastroenterol. 1996 Mar;91(3):465-7.

Reference Type BACKGROUND
PMID: 8633492 (View on PubMed)

Tamada K, Tomiyama T, Wada S, Ohashi A, Satoh Y, Ido K, Sugano K. Endoscopic transpapillary bile duct biopsy with the combination of intraductal ultrasonography in the diagnosis of biliary strictures. Gut. 2002 Mar;50(3):326-31. doi: 10.1136/gut.50.3.326.

Reference Type BACKGROUND
PMID: 11839709 (View on PubMed)

Lenz P, Eckelskemper F, Erichsen T, Lankisch T, Dechene A, Lubritz G, Lenze F, Beyna T, Ullerich H, Schmedt A, Domagk D. Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis. World J Gastroenterol. 2014 Sep 14;20(34):12260-8. doi: 10.3748/wjg.v20.i34.12260.

Reference Type DERIVED
PMID: 25232260 (View on PubMed)

Other Identifiers

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BILIARY-CANDIDIASIS_2010

Identifier Type: -

Identifier Source: org_study_id

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