Clinical trial NCT02955966: PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis
Official title: PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aspergillosis and Haematological Malignancy
Keywords: Aspergillosis
Haematological malignancy
18F-FDG PET/CT
Biomarkers
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Pasteur, Paris France
First posted: 2016-11-04
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: OPTIFIL is a pilot prospective multicenter study based over the hypothesis that the normalization of the functional imaging 18F-FDG-PET/CT during the Invasive pulmonary aspergillosis (IPA) could occur earlier than that of conventional imaging.

This study evaluates the therapeutic response through a systematic 18F-FDG-PET/CT at week 6. The latter response will be correlated with the kinetics of selected biomarkers including antigens (galactomannan, β-D glucans), circulating Aspergillus DNA and anti-Aspergillus host response markers in addition to the conventional imaging tools obtained at weeks 6 and 12.

Detailed description: Invasive pulmonary aspergillosis (IPA) is the 3rd most frequent invasive mycosis in France with a rising incidence and 40% mortality (Bitar, 2014, Lortholary, 2011). Modern antifungals (AF) improved survival of IPA but lead to ecological, toxic and cost issues. In agreement with the " plan national de la bonne maîtrise des anti-infectieux ", optimization of AF duration in IPA appears therefore challenging.

Positron emission tomography using 2-deoxy-2-\[fluorine-18\] fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT) was reported to allow shortened AF duration (Hot, 2011, Chamilos, 2008) and is currently evaluated during chronic disseminated candidiasis {CANHPARI trial, PHRC 2012, NCT01916057}. The investigators raise the hypothesis that normalization of the functional imaging 18F-FDG-PET/CT during IPA could occur earlier than that of conventional imaging. However, due to the current lack of data, an intervention trial evaluating an early AF withdrawal based on 18F-FDG-PET/CT appears premature. In order to optimize IPA treatment duration, a two-step evaluation project has been designed. The first step consists in OPTIFIL prospective project. It will evaluate the therapeutic response through a systematic 18F-FDG-PET/CT at week 6 (crucial time point (Segal) used in recent IPA trials (Marr, 2015, Maertens, 2016). The latter response will be correlated with the kinetics of selected biomarkers including antigens (galactomannan, β-D glucans), circulating Aspergillus DNA and anti-Aspergillus host response markers in addition to the conventional imaging tools obtained at weeks 6 and 12. OPTIFIL project results will serve establishing a decision algorithm used during the second step intervention trial evaluating the accuracy of IPA AF interruption.

Pilot prospective multicenter study of therapeutic follow-up of IPA in patients with hematological malignancy.

Patients will have an inclusion visit (D0) and 8 or 9 follow up visits: D3, W1, W2, W4, W6, End of Treatment, W24 and W48.

Each visit will include physical examination.

Lung CT scan, 18F-FDG-PET/CT, samplings of blood will be performed at different visits in respective centers

β-D-Glucan, Aspergillus fumigatus and Aspergillus spp. quantitative PCRs and host biomarkers such as Aspergillus Elispot will be performed and centralized

Response evaluation will be assessed by an independent committee.

CT response will be evaluated by a blinded radiologist. PET/CT response will be evaluated by 2 blinded nuclear medicine physicians.

Eligibility criteria: Inclusion Criteria:

* Patients ≥18 years-old
* Patient with hematological malignancy
* Proven or probable invasive pulmonary aspergillosis according to EORTC/MSG modified criteria
* Inclusion ≤ 4 days (≤ 5 days in case of week end) after IPA diagnosis
* Possibility to perform 18F-FDG-PET/CT scanner within the 7 subsequent days following diagnosis
* Informed consent form signed
* Affiliation to French social insurance

Exclusion Criteria:

* Pregnancy or breastfeeding women
* Life expectancy \< 3 months
* Fungal or mycobacterial lung co infection at time of IPA diagnosis
* Haematological malignancy with lung location
* Proven or probable mold infection in 6 previous months
* Disseminated aspergillosis (lung and sinus aspergillosis can be included)

Primary outcomes:
measure: Response rate according to 18F-FDG-PET/CT (PET/CT response)
timeFrame: 6 weeks
Secondary outcomes:
measure: Response rate according to EORTC/MSG criteria (Segal response).
timeFrame: 6 weeks
measure: Response rate according to EORTC/MSG criteria (Segal response).
timeFrame: 12 weeks
measure: Response rate according to PET/CT
timeFrame: 12 weeks or at the end of treatment
measure: Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions
timeFrame: 6 weeks
measure: Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions
timeFrame: 12 weeks
measure: Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions in initial work-up
timeFrame: first day
measure: Patient mortality rate
timeFrame: 6 weeks
measure: Patient mortality rate
timeFrame: 12 weeks
measure: Patient mortality rate
timeFrame: 24 weeks
measure: Patient mortality rate
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Department of Infectious Diseases and Tropical Medicine, Necker enfants malades hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Fanny LANTERNIER, Md, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivier LORTHOLARY, MD, PhD
role: STUDY_CHAIR
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