Trial Title:
Metagenomic Sequencing for the Identification of Pathogens in Febrile Neutropenic Patients
NCT ID:
NCT06075888
Condition:
Immunodepressed Patients (Hemato-oncology)
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Neutropenia
Fever
Bacteremia
Viremia
Fungemia
Antibiotic
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
Metagenomic diagnosis (mNGS, DISQVER)
Description:
Blood sample taken for metagenomic sequencing at inclusion visit.
Summary:
The development of targeted therapies and intensive protocols in oncohaematology has
improved the survival of patients with haematological malignancies. The increase in the
number of patients treated and their life expectancy has been accompanied by an increase
in the incidence of infectious complications secondary to the immunosuppression induced
by these therapies.
Febrile neutropenia (NF) is a complication that occurs in approximately 10% to 15% of
patients treated for solid tumours and up to 100% of patients treated for haematological
malignancies, particularly after bone marrow and/or haematopoietic stem cell
transplantation.
In 25% to 30% of cases, NF leads to serious complications. The vast majority of NF cases
are caused by microbial infections (bacteria, viruses, fungi, parasites, etc.), which can
progress to severe sepsis or septic shock if appropriate treatment is not initiated
rapidly (introduction of anti-infective molecules and implementation of associated
procedures). If no pathogen is identified during the management of the most severe
patients, the prognosis is poor, with a mortality rate of 10%.
The performance of diagnostic strategies is therefore an important factor in improving
the prognosis of these patients. To date, the reference diagnosis of microorganisms is
based on blood cultures, blood Polymerase Chain Reaction (PCR), β-D-glucan and
aspergillosis serology. Identifying the pathogens responsible for NF from a blood sample
without an a priori hypothesis and in an optimised timeframe could allow earlier
treatment of high-risk NF with implications for management (possible modification of
antimicrobial and/or immunosuppressive treatment).
The aim of this study is to evaluate the performance of the mNGS-DISQVER® tool in
diagnosing pathogenic microorganisms from blood samples collected from patients being
managed for high-risk NF.
Detailed description:
1. Clinical context
The development of targeted therapies and intensive protocols in oncohaematology has
improved the survival of patients with haematological malignancies. The increase in
the number of patients treated and their life expectancy has been accompanied by an
increased incidence of infectious complications secondary to the immunosuppression
induced by these therapies.
Chemotherapy-induced febrile neutropenia (NF) is a common and serious complication
occurring in approximately 10% to 15% of patients treated for solid tumours and up
to 100% of patients treated for haematological malignancies, particularly after bone
marrow transplantation. Febrile neutropenia is defined as a combination of :
- Neutropenia: neutrophil count <500 g/L or <1000 g/L (if <500 g/L is expected
within 48 hours)
- Fever: >38.5°C on a single occasion or >38°C for more than one hour. NF is
associated with high morbidity and mortality (25-30% of serious complications
and 10% of mortality). Its occurrence includes the need for hospitalisation
with broad-spectrum antibiotic therapy, delayed chemotherapy and loss of
opportunity for the patient. In the USA, an episode of NF requiring
hospitalisation is associated with an estimated health economic impact of
$19,110. A recent study in France estimated the clinical and economic impact of
hospitalisation for NF, in terms of number of patients hospitalised, number of
stays, in-hospital mortality and average cost per stay, to be €5,333 for
haemopathies.
A significant proportion of NF cases are caused by microbial infections that can
progress to septicaemia if probabilistic broad-spectrum antibiotic therapy is not
administered within an hour. Furthermore, microbiological documentation remains
essential to optimise antibiotic therapy, with blood culture as the reference test.
However, this test is limited for a number of reasons: difficulties or slowness in
culture, antibiotic treatment prior to sampling, or insufficient sample quantity.
Despite the recommended minimum of 3 or 4 pairs of blood cultures, 70% of cases of
febrile neutropenia are not microbiologically documented, making it impossible to
adapt probabilistic broad-spectrum antibiotic therapy. Another limitation is the
time required to obtain results: 6 to 24 hours are required to obtain a positive
blood culture, plus another 18 to 24 hours for bacteria to grow on solid media, and
another 18 to 24 hours for susceptibility testing (antibiotic susceptibility
testing).
The absence of an identified pathogen in the management of the most severe patients
is associated with a poor prognosis, with a mortality rate of 10%. As a result, the
performance and timeliness of diagnostic strategies are important factors in
improving the prognosis of these patients. In this context, the development of
high-throughput sequencing technologies has led to the development of new diagnostic
approaches based on the detection of circulating DNA (lcDNA, e.g. used in antenatal
screening for trisomy 21). Although more recently democratised, the concept of
microbial cDNA is well established in the field of infectious diseases. This
technology, based on a blood sample obtained by simple venipuncture, could offer
patients with febrile neutropenia an improved diagnosis, particularly in the case of
negative blood cultures, and an adjustment in their management.
2. Identification and description of the IVDD
The DISQVERⓇ device is CE-IVD marked according to the In Vitro Diagnostic Directive
(IVDD) classification approved until May 2026. The assessment file for its marking
according to In-Vitro Diagnostic Regulation (IVDR) is in progress.
DISQVER® is a digital analytical solution developed by Noscendo for the rapid
identification of microorganisms in a patient's blood sample from free circulating DNA,
without any a priori hypothesis.
The test is based on metagenomic Next Generation Sequencing "mNGS" to identify, without a
priori assumptions, the genomic sequences of micro-organisms (bacteria, DNA viruses,
fungi and parasites) potentially present in the patient's plasma sample. The genomic
sequences identified are then compared with Noscendo's proprietary database of over
16,000 microbial genome sequences, including 1,500 pathogens.
A report detailing all relevant pathogens detected in the sample is provided within a few
hours (access to a pseudonymised pdf report according to the laboratory's guidelines,
including the micro-organisms found in the highest concentration and the most likely
pathogen present).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient
- Age ≥18 years
- Being treated for solid tumour or haematological malignancy
- Presenting with high-risk febrile neutropenia (high-risk is defined by a
Multinational Association for Supportive Care in Cancer (MASCC) score ≥ 21) with an
expected duration of neutropenia ≥ 7 days. Neutropenia is defined as an absolute
neutrophil count ≤ 500/mm3. Fever is defined as temperature ≥ 38.3°C or ≥ 38°C twice
within 1 hour.
- Free, without guardianship, tutelage or subordination;
- covered by a social security scheme or by a third party;
- have given informed consent to participate in the study.
Exclusion Criteria:
- Antibiotic therapy in the 24 hours prior to enrolment, with the exception of
prophylactic use of trimethoprim-sulfamethoxazole (Cotrimoxazole) and penicillin G
(Oracillin®).
- Previous study participation
- Patients with enhanced protection, i.e. minors, persons deprived of their liberty by
a judicial or administrative decision, persons in a health or social care
institution, adults under legal protection;
- Pregnant or lactating women of childbearing age (menopause must be documented) who
refuse or do not have an effective method of contraception (hormonal/mechanical: per
os, injectable, transcutaneous, implantable, intrauterine device or surgical: tubal
ligation, hysterectomy, total oophorectomy) for the duration of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
C.H.U. d'Angers
Address:
City:
Angers
Zip:
49933
Country:
France
Status:
Recruiting
Contact:
Last name:
CORENTIN ORVAIN, MD
Phone:
+33241356451
Email:
corentin.orvain@chu-angers.fr
Facility:
Name:
CHU de Brest
Address:
City:
Brest
Zip:
29606
Country:
France
Status:
Recruiting
Contact:
Last name:
ANNE-MARIE COUTURIER, MD
Phone:
+33292020162
Email:
marie-anne.couturier@chu-brest.fr
Facility:
Name:
C.H.U. de Limoges
Address:
City:
Limoges
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
TURLURE Pascal, MD
Phone:
+33 5 55 05 88 62
Email:
Pascal.Turlure@chu-limoges.fr
Facility:
Name:
C.H.U. de Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Status:
Recruiting
Contact:
Last name:
NIELS MOYA, MD
Phone:
+33549445643
Email:
niels.moya@chu-poitiers.fr
Facility:
Name:
C.H.U. de Tours
Address:
City:
Tours
Zip:
37044
Country:
France
Status:
Recruiting
Contact:
Last name:
ALBAN VILATTE, MD
Phone:
+33247477092
Email:
a.villate@chu-tours.fr
Start date:
January 12, 2024
Completion date:
January 12, 2025
Lead sponsor:
Agency:
Poitiers University Hospital
Agency class:
Other
Collaborator:
Agency:
Noscendo
Agency class:
Other
Source:
Poitiers University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06075888
