Hepatosplenic CANdidiasis : PETscan and Immune Response Analysis (CANHPARI)

Multicenter Prospective Pilot Study Investigating Pathophysiology, Diagnostic and Therapeutic Strategies of Hepatosplenic Candidiasis

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.

Study Overview

• Status: Completed
• Conditions: Neutropenia; Hematopoietic Stem Cell Transplantation; Hematological Malignancies; Invasive Fungal Disease; Chronic Disseminated Candidiasis
• Intervention / Treatment: Device: 18F-FDG PET Scan

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants Malades,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 18F-FDG PET Scan; 18F-FDG PET Scan at Day 0 and M3	Device: 18F-FDG PET Scan; to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global response to therapy	Clinical assessment (no fever) and PET scan assessment (intensity of liver and/or spleen lesions)	at month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-FDG PET scan and RMI usefulness in initial diagnosis	Comparison between Day 0 and Month 3 exams	at month 3
Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls. Assessment of a new real-time PCR on serum and hepatic tissue	at day 0
Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls. Assessment of a new real-time PCR on serum and hepatic tissue	at Month 3
Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls. Assessment of a new real-time PCR on serum and hepatic tissue	at Month 6
Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at day 0
Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at month 3
Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at month 6
Genetic susceptibility	Search for susceptibility genes to candidiasis in comparison with controls	at day 0

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Institut Pasteur; University of Lausanne Hospitals; University Hospital, Lille; Unité de Recherche Clinique Necker Cochin, France

Publications and helpful links

General Publications

• Candon S, Rammaert B, Foray AP, Moreira B, Gallego Hernanz MP, Chatenoud L, Lortholary O. Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells. J Infect Dis. 2020 May 11;221(11):1907-1916. doi: 10.1093/infdis/jiz688.
• Rammaert B, Maunoury C, Rabeony T, Correas JM, Elie C, Alfandari S, Berger P, Rubio MT, Braun T, Bakouboula P, Candon S, Montravers F, Lortholary O. Does 18F-FDG PET/CT add value to conventional imaging in clinical assessment of chronic disseminated candidiasis? Front Med (Lausanne). 2022 Dec 20;9:1026067. doi: 10.3389/fmed.2022.1026067. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: August 2, 2013
• First Submitted That Met QC Criteria: August 2, 2013
• First Posted (Estimated): August 5, 2013

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Genotype; Fluorodeoxyglucose F18; Real-Time Polymerase Chain Reaction; Immune Reconstitution Inflammatory Syndrome; Genetic Susceptibility; Positron-Emission Tomography Scan; Enzyme-Linked Immunospot Assay; beta-1,3-D-glucan; Candida spp.
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Immune System Diseases; Infections; Leukocyte Disorders; Hematologic Diseases; Bacterial Infections and Mycoses; Leukopenia; Agranulocytosis; Disease Susceptibility; Mycoses; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Invasive Fungal Infections; Hematologic Neoplasms; Neutropenia; Genetic Predisposition to Disease; Immune Reconstitution Inflammatory Syndrome; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: P120115; AOM12047

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No