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PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis (OPTIFIL)

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ClinicalTrials.gov Identifier: NCT02955966
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
Institut Pasteur, Paris France
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Aspergillosis and Haematological Malignancy Device: imaging 18F-FDG-PET/CT Biological: Blood collection Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: PET/CT Guided Antifungal Stewardship in Invasive Pulmonary Aspergillosis
Actual Study Start Date : June 2, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Aspergillosis

Arm Intervention/treatment
Experimental: Patient with invasive pulmonary aspergillosis
Blood collection and imaging 18F-FDG-PET/CT
Device: imaging 18F-FDG-PET/CT
18F-FDG PET Scan at Day 0, W6 and W12

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




Primary Outcome Measures :
  1. Response rate according to 18F-FDG-PET/CT (PET/CT response) [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Response rate according to EORTC/MSG criteria (Segal response). [ Time Frame: 6 weeks ]
  2. Response rate according to EORTC/MSG criteria (Segal response). [ Time Frame: 12 weeks ]
  3. Response rate according to PET/CT [ Time Frame: 12 weeks or at the end of treatment ]
  4. Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions [ Time Frame: 6 weeks ]
  5. Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions [ Time Frame: 12 weeks ]
  6. Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions in initial work-up [ Time Frame: first day ]
  7. Patient mortality rate [ Time Frame: 6 weeks ]
    overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies

  8. Patient mortality rate [ Time Frame: 12 weeks ]
    overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies

  9. Patient mortality rate [ Time Frame: 24 weeks ]
    overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies

  10. Patient mortality rate [ Time Frame: 48 weeks ]
    overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955966


Contacts
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Contact: Fanny LANTERNIER, MD, PhD +33 (0)1 44 49 52 62 fanny.lanternier@aphp.fr
Contact: Prissile BAKOUBOULA, PhD +33 1 71 19 64 94 prissile.bakouboula@aphp.fr

Locations
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France
Department of Infectious Diseases and Tropical Medicine, Necker enfants malades hospital Recruiting
Paris, France, 75015
Contact: Fanny LANTERNIER, Md, PhD    +33 (0)1 44 49 52 62    fanny.lanternier@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut Pasteur, Paris France
Investigators
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Principal Investigator: Fanny LANTERNIER, Md, PhD Assistance Publique - Hôpitaux de Paris
Study Chair: Olivier LORTHOLARY, MD, PhD Assistance Publique - Hôpitaux de Paris

Publications:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02955966     History of Changes
Other Study ID Numbers: P150916
2016-A00408-43 ( Registry Identifier: IDRCB )
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Aspergillosis
Haematological malignancy
18F-FDG PET/CT
Biomarkers
Additional relevant MeSH terms:
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Aspergillosis
Pulmonary Aspergillosis
Invasive Pulmonary Aspergillosis
Hematologic Neoplasms
Neoplasms
Mycoses
Neoplasms by Site
Hematologic Diseases
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Invasive Fungal Infections
Antifungal Agents
Miconazole
Fluorodeoxyglucose F18
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP3A Inhibitors