PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis

Not Applicable

Completed

• Conditions: Aspergillosis and Haematological Malignancy
• Interventions: Device: imaging 18F-FDG-PET/CT; Biological: Blood collection

• Registration Number: NCT02955966
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2016-11-03
• Study First Submitted QC: 2016-11-03
• Study First Posted: 2016-11-04
• Study Start: 2017-06-02
• Primary Completion: 2022-05-02
• Study Completion: 2022-05-02
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-10
• Last Update Posted: 2022-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patient with invasive pulmonary aspergillosis	imaging 18F-FDG-PET/CT	Blood collection and imaging 18F-FDG-PET/CT
Patient with invasive pulmonary aspergillosis	Blood collection	Blood collection and imaging 18F-FDG-PET/CT

Primary Outcome Measures

Name	Time	Method
Response rate according to 18F-FDG-PET/CT (PET/CT response)	6 weeks

Secondary Outcome Measures

Name	Time	Method
Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions	12 weeks
Response rate according to EORTC/MSG criteria (Segal response).	12 weeks
Patient mortality rate	48 weeks	overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies
Response rate according to PET/CT	12 weeks or at the end of treatment
Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions in initial work-up	first day

Trial Locations

Locations (1)

Department of Infectious Diseases and Tropical Medicine, Necker enfants malades hospital; 🇫🇷 Paris, France