Clinical trial NCT02509884: Long-term Results of Comprehensive AE Management
Official title: Comprehensive Diagnosis and Treatment of Alveolar Echinococcosis : A Single-center, Longterm Observational Study of 312 Patients in Germany
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alveolar Echinococcosis
Keywords: Alveolar Echinococcosis (AE)
Echinococcus multilocularis
antiparasitic treatment
surgery
classification
staging
prospective cohort study
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2015-07-28
Enrollment: 312
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with AE seen at the specialized treatment unit in Ulm between January 1992 and December 2011 were included in the database. Follow-up ended on 31.12.2012. Cases were defined according to the likelihood of diagnosis as a "possible", "probable", or "confirmed case"

Brief summary: Comprehensive diagnosis and treatment of Alveolar Echinococcosis : A single-center, long-term observational study of 312 Patients in Germany. Human alveolar echinococcosis (AE) is the most Iethal human helminthic infection and is one of the 17 neglected tropical diseases prioritized by the World Health Organization (WHO). Its incidence is low in endemic regions of Central and Western Europe (0.03-0.05/100,000), but morbidity and treatment costs are high. In this observational study, the investigators assessed the severity of the disease using the PNM staging system and report on the long-term results of specific AE therapy in an interdisciplinary team of clinicians.

Detailed description: All patients with Alveolar Echinococcosis (AE) seen at the specialized treatment unit in Ulm between January 1992 and December 2011 were included in the database. Follow up ended on 31.12.2012. Cases were defined to the likelihood of diagnosis as a "possible", "probable" or "confirmed" case . Diagnosis of AE was based on clinical presentation, epidemiological history, pathognomonic imaging findings, specific laboratory results, such as immunodiagnosis or histopathological findings in resected/ biopsied specimens, and/or detection of nucleic acid sequences in such specimens. The location of the larval lesions and its spread at diagnosis was documented using the PNM classification. Treatment with benzimidazoles was followed the WHO-IWGE recommendations. Treatment efficacy was monitored by US examination and FDG-PET scan or MRI. To categorize each case at each visit the terms "cured", "stable" or "progressive" were used. Patients' data was assessed at each visit; missing information was obtained from hospital records or the family doctor. Names were anonymized and data was stored in a Microsoft Excel database. Statistics were done with SAS version 9.3.

The data were stratified into series A containing diagnoses until December 1999 and series B from January 2000 onwards. This separation was chosen as patient admissions to the clinic rose almost 3-fold in 2000 when notification of AE became mandatory in Germany. It can be assumed that series B better represents AE patient characteristics, disease manifestation and comprehensive management; series A includes case histories with favorable prognoses at the time of diagnosis while optimal treatment for AE was still unavailable.

Outcome parameters for this study population were: overall survival after diagnosis, relapse after surgery or progression of remaining liver lesions in size or new lesions in other organs, and time to relapse or progress. Survival was estimated by the Kaplan Meier method.

Parameters with an assumed influence on the time until relapse or progress of the parasitic lesions entered Kaplan Meier survival analysis and Cox proportional hazard regression model analysis, respectively, and hazard ratios (HR) with corresponding 95% confidence intervals (CI) were calculated. Logistic regression was used to identify factors which may predict a successful treatment interruption using the odds ratio (OR) as an appropriate outcome parameter.

Eligibility criteria: Inclusion Criteria:

* All patients with AE seen at the specialized treatment unit in Ulm between January 1992 and December 2011.

Primary outcomes:
measure: Overall survival after diagnosis,
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012 .Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
measure: Relapse after surgery or progression of remaining liver lesions in size or new lesions in other organs
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012.Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
measure: Time to relapse or progress
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012.Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
Secondary outcomes:
measure: Symptoms and comorbidities
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012. Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
measure: Medical treatment and side effects
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
measure: Treatment interruption ant potential cure
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012.Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
measure: Surgical and interventional treatment
timeFrame: inclusion January 1992-December 2011; end of follow-up December 2012.Inclusion January 1992-December 1999 (series A).Inclusion January 2000- December 2011 (series B)
Other outcomes:
Locations:
Study officials:
affiliation: University of Ulm
name: Beate Grüner, MD
role: STUDY_CHAIR
References:
citation: Kern P, Wen H, Sato N, Vuitton DA, Gruener B, Shao Y, Delabrousse E, Kratzer W, Bresson-Hadni S. WHO classification of alveolar echinococcosis: principles and application. Parasitol Int. 2006;55 Suppl:S283-7. doi: 10.1016/j.parint.2005.11.041. Epub 2005 Dec 15.
citation: Brunetti E, Kern P, Vuitton DA; Writing Panel for the WHO-IWGE. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010 Apr;114(1):1-16. doi: 10.1016/j.actatropica.2009.11.001. Epub 2009 Nov 30.