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Trial record 1 of 1 for:    NCT03349931
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Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis (MYCOGENIE)

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ClinicalTrials.gov Identifier: NCT03349931
Recruitment Status : Unknown
Verified April 2018 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was:  Recruiting
First Posted : November 22, 2017
Last Update Posted : May 1, 2018
Sponsor:
Collaborator:
Société ADEMTECH SA
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date November 17, 2017
First Posted Date November 22, 2017
Last Update Posted Date May 1, 2018
Actual Study Start Date February 5, 2018
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 17, 2017)
Performance of PCR for Aspergillosis diagnosis [ Time Frame: 6 months ]
Determination of the performances (Sensitivity, specificity, PPV and NPV) of the kit
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 17, 2017)
Detection of azole resistance [ Time Frame: 6 months ]
Detection of TR34 and L98H mutations in the A. fumigatus single-copy number gene cyp51A.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis
Official Title Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis in Hematological Patients
Brief Summary 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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Human sera (serum)
Sampling Method Non-Probability Sample
Study Population Hematological patients at high risk for invasive aspergillosis, who can be classified according to EORTC criteria
Condition Invasive Aspergillosis in Patients With Onco-haematological Diseases
Intervention Diagnostic Test: DNA extraction and detection of Aspergillus fumigatus in serum samples
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).
Study Groups/Cohorts Hematological patients
Hematological patients at high risk for invasive aspergillosis
Intervention: Diagnostic Test: DNA extraction and detection of Aspergillus fumigatus in serum samples
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: November 17, 2017)
420
Original Estimated Enrollment Same as current
Estimated Study Completion Date April 2019
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT03349931
Other Study ID Numbers K-170102
2017-A01518-45 ( Registry Identifier: ID-RCB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor Assistance Publique - Hôpitaux de Paris
Collaborators Société ADEMTECH SA
Investigators
Principal Investigator: Eric DANNAOUI, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Marie-Elisabeth BOUGNOUX, MD, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date April 2018