Clinical trial NCT01916057: Hepatosplenic CANdidiasis : PETscan and Immune Response Analysis
Official title: Multicenter Prospective Pilot Study Investigating Pathophysiology, Diagnostic and Therapeutic Strategies of Hepatosplenic Candidiasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Invasive Fungal Disease
Chronic Disseminated Candidiasis
Hematological Malignancies
Hematopoietic Stem Cell Transplantation
Neutropenia
Keywords: Positron-Emission Tomography Scan
Fluorodeoxyglucose F18
Magnetic Resonance Imaging
Enzyme-Linked Immunospot Assay
Immune Reconstitution Inflammatory Syndrome
Real-Time Polymerase Chain Reaction
beta-1,3-D-glucan
Candida spp.
Genetic Susceptibility
Genotype
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: University of Lausanne Hospitals
name: University Hospital, Lille
name: Institut Pasteur
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2013-08-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

Detailed description: Chronic disseminated candidiasis, often referred to as hepatosplenic candidiasis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients with profound and prolonged neutropenia, which is more often seen in patients with hematologic malignancies. Despite an appropriate antifungal prophylaxis, the incidence of HSC in France might be closed to 5% in patients suffering from acute leukemia. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. Current guidelines recommend a 6-month duration treatment. Prolonged treatments up to 6 months are frequent, leading to antifungal toxicity and cost increase. Preliminary study by our team has already assessed F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) as a diagnostic tool for HSC. 18F-FDG PET scan could be helpful in the diagnosis, follow-up and therapy strategy of HSC, helping to stop antifungal treatment. Other molecular, immunological and serological tools have to be developed in order to avoid hepatic biopsies. Actually, mycological evidence of infection is found in only 20% of the cases. The pathogenesis of HSC is also not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome (IRIS). In that context, a better understanding of the disease pathophysiology and of the potential genetic susceptibility could have an impact on therapy strategy. For example, new approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This study is the first step to improve HSC diagnosis and therapy strategy.

Eligibility criteria: Patients' inclusion criteria:

* Adults aged ≥18 years-old
* Hospitalized for hematological malignancy or hematopoietic stem cell transplantation
* Recent (\>2months), prolonged (\>10 days), profound (\>100 PMN/mm3), feverish neutropenia
* Suspected hepatosplenic candidiasis (typical small nodular lesions on abdominal RMI or CT)

Patients' exclusion criteria:

- hepatosplenic lesions of other proven origin

Patients' non-inclusion criteria:

* Life expectancy \>3 months
* Pregnancy
* HIV infection
* Hepatic biopsy within 3 weeks before 18F-FDG PET scan

Primary outcomes:
measure: Global response to therapy
timeFrame: at month 3
Secondary outcomes:
measure: 18F-FDG PET scan and RMI usefulness in initial diagnosis
timeFrame: at month 3
measure: Serological and molecular mycological tools assessment
timeFrame: at day 0
measure: Serological and molecular mycological tools assessment
timeFrame: at Month 3
measure: Serological and molecular mycological tools assessment
timeFrame: at Month 6
measure: Inflammatory cells and mediators
timeFrame: at day 0
measure: Inflammatory cells and mediators
timeFrame: at month 3
measure: Inflammatory cells and mediators
timeFrame: at month 6
measure: Genetic susceptibility
timeFrame: at day 0
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants Malades,
Study officials:
References: