Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis (MYCOGENIE)

December 3, 2020 updated by: Assistance Publique - Hôpitaux de Paris

Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis in Hematological Patients

The purpose of this study is to evaluate the performances of the real-time PCR ADEMTECH kit of DNA extraction and detection of Aspergillus fumigatus in serum samples in patients at high-risk for invasive aspergillosis (IA). DNA detection will be associated with detection of TR34/L98H mutations in cyp51A gene, which confer azole resistance.

Study Overview

Detailed Description

Accurate diagnosis of invasive pulmonary aspergillosis (IPA) in patients at high risk of invasive fungal infection remains challenging due to difficulties in differentiating IPA from pulmonary infections caused by other molds or bacteria on clinical and radiological grounds. Therefore, culture-based microbiological diagnosis is of primary importance but requires semi-invasive or invasive procedures, such as bronchoalveolar Lavage (BAL) or computed-tomography (CT)-guided needle biopsy.

Alternate diagnostic methods include the detection of biomarkers, such as fungal antigens (Aspergillus galactomannan [GM]) or DNA released by Aspergillus hyphae in host tissues. These biomarkers are well recognized as early IPA predictors Recently, several clinical evaluations to detect Aspergillus DNA, either in respiratory or in blood-based samples, have clearly shown the diagnostic value of this biomarker. In addition, methodological recommendations have been established for PCR protocols, and different standardized Aspergillus quantitative PCR (qPCR) kits have been commercialized. These recent advances show that PCR is now mature for routine use in clinical settings.

Another issue is the emergence of aspergillosis due to azole-resistant isolates. Acquired azole resistance in A. fumigatus has been reported since 1997 and has emerged in many countries, particularly in Europe, as well as on other continents. In some instances, acquired resistance may be driven by antifungal selection in patients receiving long-term therapy. Nevertheless, it seems that many azole-resistant strains originated in the environment due to selection by azole fungicides used in agriculture. Azole resistance in A. fumigatus is associated mainly with mutations in the cyp51A gene, and among several mutations described, the most frequent is the mutation comprising a 34-bp tandem repeat (TR34) and the L98H alteration. Since azoles are the recommended first-line treatment for IPA, the emergence of azole resistance is worrisome and has been shown to be associated with an increased rate of clinical failure. For these reasons, routine antifungal susceptibility testing of clinical isolates has been recommended recently. Nevertheless, isolates are not always retrieved in culture, particularly for patients with hematological malignancies. Therefore, molecular detection of resistance may be a major advance for the management of patients with invasive aspergillosis.

The aim of this study will be to validate the new MycoGENIE A. fumigatus real-time PCR kit and to evaluate its performance on clinical samples for the detection of A. fumigatus and its azole resistance. This multiplex assay detects DNA from the A. fumigatus species complex by targeting the multicopy 28S rRNA gene and specific TR34 and L98H mutations in the single-copy number cyp51A gene of A. fumigatus.

The study will be performed in hematological patients with high-risk of developping IA during the course of chemotherapy. In these patients, bi-weekly detection of GM is routinely performed in all centers in France. The PCR will be performed on the samples used for GM detection. DNA will be extracted according to the manufacturer's protocol, using the MycoGENIE kit for AutoMag solution. Real-time PCR for the detection of A. fumigatus DNA will be performed using the MycoGENIE A. fumigatus real-time PCR kit (Ademtech, Pessac, France).

AI will be defined as proven or probable aspergillosis, according to EORTC criteria.

For each patient, clinical data will be collected in each center. These data include: EORTC classification, type and duration of antifungal treatments, results of GM tests, results of mycological cultures, and results of PCR tests (positivity and Ct values). For each patient a case report form (CRF) will be filled and transfered to the investigating center for analysis. Sensitivity, specificity, PPV and NPV of the PCR test will be calculated.

Study Type

Observational

Enrollment (Actual)

350

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

      • Bordeaux, France, 33000
        • CHU Bordeaux, Groupe hospitalier
      • Dijon, France, 21000
        • CHU de DIJON, Hôpital du bocage
      • Lille, France, 59000
        • CHRU de Lille, Hopital Claude Huriez
      • Nantes, France, 44000
        • CHU de Nantes, Hôpital de Moncousu
      • Paris, France, 75015
        • Hôpital Necker - Enfants maladies (AP-HP)
      • Rennes, France, 35000
        • CHU de Rennes, Hopital de Pontchaillou

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Hematological patients at high risk for invasive aspergillosis, who can be classified according to EORTC criteria

Description

Inclusion Criteria:

  1. Adult Patients (≥ 18 years) hospitalized in onco hematologic unit or in hematopoietic stem cell transplantation (HSCT) unit
  2. Patients with acute leukemia undergoing induction for AML, ALL, chimotherapy with neutopenia >10 days or Patients undergoing allogeneic stem cell chemotherapy transplantation
  3. Patients with biweekly screening for GM detection in serum

Exclusion Criteria:

  1. Patient < 18 years-old (minor)
  2. Informed consent not available
  3. Patient without affiliation to French social insurance
  4. Patient without biweekly screening for GM detection in serum

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Hematological patients
Hematological patients at high risk for invasive aspergillosis
Performances diagnostic test of the real-time PCR ADEMTECH kit of DNA extraction and detection of Aspergillus fumigatus in serum samples in patients at high-risk for invasive aspergillosis (IA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Performance of PCR for Aspergillosis diagnosis
Time Frame: 6 months
Determination of the performances (Sensitivity, specificity, PPV and NPV) of the kit
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of azole resistance
Time Frame: 6 months
Detection of TR34 and L98H mutations in the A. fumigatus single-copy number gene cyp51A.
6 months

Collaborators and Investigators

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

Collaborators

Investigators

  • Principal Investigator: Eric DANNAOUI, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Principal Investigator: Marie-Elisabeth BOUGNOUX, 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.

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)

February 5, 2018

Primary Completion (Actual)

January 20, 2020

Study Completion (Actual)

January 20, 2020

Study Registration Dates

First Submitted

November 17, 2017

First Submitted That Met QC Criteria

November 17, 2017

First Posted (Actual)

November 22, 2017

Study Record Updates

Last Update Posted (Actual)

December 4, 2020

Last Update Submitted That Met QC Criteria

December 3, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • K-170102
  • 2017-A01518-45 (Registry Identifier: ID-RCB)

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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