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

October 10, 2022 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

51

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Department of Infectious Diseases and Tropical Medicine, Necker enfants malades hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate according to 18F-FDG-PET/CT (PET/CT response)
Time Frame: 6 weeks
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate according to EORTC/MSG criteria (Segal response).
Time Frame: 6 weeks
6 weeks
Response rate according to EORTC/MSG criteria (Segal response).
Time Frame: 12 weeks
12 weeks
Response rate according to PET/CT
Time Frame: 12 weeks or at the end of treatment
12 weeks or at the end of treatment
Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions
Time Frame: 6 weeks
6 weeks
Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions
Time Frame: 12 weeks
12 weeks
Number of patients for whom 18F-FDG-PET/CT has evidenced extra pulmonary attributable lesions in initial work-up
Time Frame: first day
first day
Patient mortality rate
Time Frame: 6 weeks
overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies
6 weeks
Patient mortality rate
Time Frame: 12 weeks
overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies
12 weeks
Patient mortality rate
Time Frame: 24 weeks
overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies
24 weeks
Patient mortality rate
Time Frame: 48 weeks
overall mortality and relationship with Invasive Pulmonary Aspergillosis or Haematological Malignancies
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut Pasteur, Paris France

Investigators

  • Study Chair: Olivier LORTHOLARY, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Principal Investigator: Fanny LANTERNIER, Md, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 2, 2017

Primary Completion (Actual)

May 2, 2022

Study Completion (Actual)

May 2, 2022

Study Registration Dates

First Submitted

November 3, 2016

First Submitted That Met QC Criteria

November 3, 2016

First Posted (Estimate)

November 4, 2016

Study Record Updates

Last Update Posted (Actual)

October 12, 2022

Last Update Submitted That Met QC Criteria

October 10, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P150916
  • 2016-A00408-43 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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