PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis

NCT ID: NCT02955966

Last Updated: 2025-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-02

Study Completion Date

2022-05-02

Brief Summary

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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

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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.

Conditions

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Aspergillosis and Haematological Malignancy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Patient with invasive pulmonary aspergillosis

Blood collection and imaging 18F-FDG-PET/CT

Group Type EXPERIMENTAL

imaging 18F-FDG-PET/CT

Intervention Type DEVICE

18F-FDG PET Scan at Day 0, W6 and W12

Blood collection

Intervention Type BIOLOGICAL

Blood collection at D0, D3, W1, W2, W4, W6, W12, end of treatment.

Interventions

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imaging 18F-FDG-PET/CT

18F-FDG PET Scan at Day 0, W6 and W12

Intervention Type DEVICE

Blood collection

Blood collection at D0, D3, W1, W2, W4, W6, W12, end of treatment.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut Pasteur, Paris France

UNKNOWN

Sponsor Role collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fanny LANTERNIER, Md, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Olivier LORTHOLARY, MD, PhD

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Locations

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Department of Infectious Diseases and Tropical Medicine, Necker enfants malades hospital

Paris, Paris, France

Site Status

Countries

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France

References

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Baxter CG, Marshall A, Roberts M, Felton TW, Denning DW. Peripheral neuropathy in patients on long-term triazole antifungal therapy. J Antimicrob Chemother. 2011 Sep;66(9):2136-9. doi: 10.1093/jac/dkr233. Epub 2011 Jun 17.

Reference Type BACKGROUND
PMID: 21685202 (View on PubMed)

Herbrecht R, Caillot D, Cordonnier C, Auvrignon A, Thiebaut A, Brethon B, Michallet M, Mahlaoui N, Bertrand Y, Preziosi P, Ruiz F, Gorin NC, Gangneux JP. Indications and outcomes of antifungal therapy in French patients with haematological conditions or recipients of haematopoietic stem cell transplantation. J Antimicrob Chemother. 2012 Nov;67(11):2731-8. doi: 10.1093/jac/dks266. Epub 2012 Jul 31.

Reference Type BACKGROUND
PMID: 22850692 (View on PubMed)

Lortholary O, Gangneux JP, Sitbon K, Lebeau B, de Monbrison F, Le Strat Y, Coignard B, Dromer F, Bretagne S; French Mycosis Study Group. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005-2007). Clin Microbiol Infect. 2011 Dec;17(12):1882-9. doi: 10.1111/j.1469-0691.2011.03548.x. Epub 2011 Jun 10.

Reference Type BACKGROUND
PMID: 21668573 (View on PubMed)

Bitar D, Lortholary O, Le Strat Y, Nicolau J, Coignard B, Tattevin P, Che D, Dromer F. Population-based analysis of invasive fungal infections, France, 2001-2010. Emerg Infect Dis. 2014 Jul;20(7):1149-55. doi: 10.3201/eid2007.140087.

Reference Type BACKGROUND
PMID: 24960557 (View on PubMed)

Epaulard O, Villier C, Ravaud P, Chosidow O, Blanche S, Mamzer-Bruneel MF, Thiebaut A, Leccia MT, Lortholary O. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study. Clin Infect Dis. 2013 Dec;57(12):e182-8. doi: 10.1093/cid/cit600. Epub 2013 Sep 17.

Reference Type BACKGROUND
PMID: 24046296 (View on PubMed)

Tedja R, El-Sherief A, Olbrych T, Gordon S. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. Transpl Infect Dis. 2013 Aug;15(4):424-9. doi: 10.1111/tid.12088. Epub 2013 May 13.

Reference Type BACKGROUND
PMID: 23663268 (View on PubMed)

Moon WJ, Scheller EL, Suneja A, Livermore JA, Malani AN, Moudgal V, Kerr LE, Ferguson E, Vandenberg DM. Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain. Clin Infect Dis. 2014 Nov 1;59(9):1237-45. doi: 10.1093/cid/ciu513. Epub 2014 Jul 3.

Reference Type BACKGROUND
PMID: 24992954 (View on PubMed)

Hot A, Maunoury C, Poiree S, Lanternier F, Viard JP, Loulergue P, Coignard H, Bougnoux ME, Suarez F, Rubio MT, Mahlaoui N, Dupont B, Lecuit M, Faraggi M, Lortholary O. Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections. Clin Microbiol Infect. 2011 Mar;17(3):409-17. doi: 10.1111/j.1469-0691.2010.03301.x.

Reference Type BACKGROUND
PMID: 20636432 (View on PubMed)

Chamilos G, Macapinlac HA, Kontoyiannis DP. The use of 18F-fluorodeoxyglucose positron emission tomography for the diagnosis and management of invasive mould infections. Med Mycol. 2008 Feb;46(1):23-9. doi: 10.1080/13693780701639546.

Reference Type BACKGROUND
PMID: 18297544 (View on PubMed)

Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, Heinz WJ, Jagannatha S, Koh LP, Kontoyiannis DP, Lee DG, Nucci M, Pappas PG, Slavin MA, Queiroz-Telles F, Selleslag D, Walsh TJ, Wingard JR, Maertens JA. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015 Jan 20;162(2):81-9. doi: 10.7326/M13-2508.

Reference Type BACKGROUND
PMID: 25599346 (View on PubMed)

Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566.

Reference Type BACKGROUND
PMID: 18637757 (View on PubMed)

Other Identifiers

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2016-A00408-43

Identifier Type: REGISTRY

Identifier Source: secondary_id

P150916

Identifier Type: -

Identifier Source: org_study_id

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