Secondary CholangitisNCT01109550
Biliary Candidiasis - Optimization of Diagnostics and Therapy
An observational study of Secondary Cholangitis and Bile Duct Strictures of Unknown Origin, run by University Hospital Muenster at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Secondary Cholangitis, Bile Duct Strictures of Unknown Origin
- What is being tested?
- ERCP
- Type of treatment
- Surgery or procedure
- How many people
- 123 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2011to Nov 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients referred to a hospital of maximum care.
Who may be able to join
- Secondary cholangitis
- Bile duct strictures of unknown origin
- Age ≥ 18 years
- All individuals provide written informed consent before entering the trial
Who cannot join
- Exclusion criteria and contraindications of the performed procedure
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Unitersity Hospital of Muenster, Department of Medicine B
Münster, 48149
About this study
Official title: Biliary Candidiasis - Evaluation of Risk Factors, Implementation of an Algorithm in Diagnostics and Therapy
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.
Read the detailed description
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.
- Being tested
- ERCP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERCPProcedure or surgery
endoscopic retrograde cholangiopancreatography transpapillary biopsies
| Study group | Role | What they receive |
|---|---|---|
| with biliary candidiasis | Patients with positive fungal cultures of bile samples. Receives: Procedure: ERCP | |
| without biliary candidiasis | Patients with negative fungal cultures of bile samples. Receives: Procedure: ERCP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnosis of an invasive fungal infection of the biliary tract
Diagnosis of an invasive fungal infection of the biliary tract
Measured: 12 month
Secondary outcomes (1)
Evaluation of risk factors 2. Implementation of an algorithm in diagnostics and therapy
Risk factors
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2010 (estimated)
- Study startApr 2011
- Primary completionOct 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Secondary CholangitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Philipp Lenz, M.D., Study chair, University Hospital of MuensterDirk Domagk, M.D., Study chair, University Hospital of Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01109550
- Sponsor's protocol ID
- BILIARY-CANDIDIASIS_2010
- Status last verified
- Dec 2012
- First submitted
- 21 Apr 2010
- Last updated
- 28 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 1928197Bouche 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.
PubMed 8445217Domagk 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.
PubMed 17029620George 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.
PubMed 15727737Singh 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.
PubMed 11792979Wig 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.
PubMed 9830582Domagk 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.
PubMed 11336173Lenz 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.
PubMed 19555935Domagk 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.
PubMed 12117887Kubota 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.
PubMed 8213710Sugiyama 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.
PubMed 8633492Tamada 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.
PubMed 11839709Lenz 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.
PubMed 25232260
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biliary Candidiasis - Evaluation of Risk Factors, Implementation of an Algorithm in Diagnostics and Therapy
- ClinicalTrials.gov ID
- NCT01109550
- Acronym / sponsor ID
- BILIARY-CANDIDIASIS_2010
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2011 (actual)
- Primary completion
- Oct 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 23 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| with biliary candidiasis | – | Procedure: ERCPPatients with positive fungal cultures of bile samples. |
| without biliary candidiasis | – | Procedure: ERCPPatients with negative fungal cultures of bile samples. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients referred to a hospital of maximum care.
Key inclusion criteria (4 listed)
- Secondary cholangitis
- Bile duct strictures of unknown origin
- Age ≥ 18 years
- All individuals provide written informed consent before entering the trial
Key exclusion criteria (7 listed)
- Exclusion criteria and contraindications of the performed procedure
- Ineffective aspiration of bile samples
- Pregnant or breastfeeding patient
- Age < 18 years
- Missing informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERCPendoscopic retrograde cholangiopancreatography transpapillary biopsies | Procedure or surgery | with biliary candidiasis, without biliary candidiasis |
Primary outcome
Diagnosis of an invasive fungal infection of the biliary tract
Time frame: 12 month
Diagnosis of an invasive fungal infection of the biliary tract
1 secondary outcome
Evaluation of risk factors 2. Implementation of an algorithm in diagnostics and therapy
Time frame: 12 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
- Background: PubMed 1928197Banerjee 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.
- Background: PubMed 8445217Bouche 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.
- Background: PubMed 17029620Domagk 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.
- Background: PubMed 15727737George 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.
- Background: PubMed 11792979Singh 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.
- Background: PubMed 9830582Wig 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.
- Background: PubMed 11336173Domagk 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.
- Background: PubMed 19555935Lenz 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.
- Background: PubMed 12117887Domagk 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.
- Background: PubMed 8213710Kubota 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.
- Background: PubMed 8633492Sugiyama 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.
- Background: PubMed 11839709Tamada 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.
Related trials for Secondary Cholangitis
Active, not recruitingObservational study
Secondary Sclerosis Cholangitis Prospective
Secondary Sclerosis Cholangitis in Critically Ill Patients
Active, not recruitingObservational study
Secondary Sclerosing Cholangitis in Critically Ill Patients
Secondary Sclerosing Cholangitis
RecruitingObservational study
Prospective Cohort of Immune Checkpoint Inhibitor-induced Hepatitis
Liver Injury, Secondary to Immune Checkpoint Inhibitors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philipp Lenz, M.D. study chair
University Hospital of Muenster
Dirk Domagk, M.D. study chair
University Hospital of Muenster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Secondary Cholangitis and Bile Duct Strictures of Unknown Origin, run by University Hospital Muenster at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnosis of an invasive fungal infection of the biliary tract (time frame: 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01109550, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2022.