Detection of Azole Resistance Inducing Mutations on DNA Extracted Directly From Serum or Plasma of Immunocompromised Patients With an Invasive Aspergillus Infection Azole Resistance PCR Optimalization-study

NCT06069505 | Recruiting

• 2 other identifiers: NL62004.078.17MEC-2017-391
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Invasive aspergillosis (IA) is the most common mould infection in immunocompromised patients with haematological disease. Voriconazole, a triazole, improves overall survival of patients with an IA and is the mainstay of therapy. Resistance of A. Fumigatus emerged as an important clinical problem and infections with azole resistant Aspergillus have a high mortality. Nowhere in the world, azole resistance is more prevalent than in the Netherlands. Rapid detection of resistance is key to improve the patient's outcome but fungal cultures take time and are often negative. The investigators aim to detect azole resistance associated mutations in fungal DNA extracted directly from serum or plasma to accelerate diagnosis and improve outcome of patients infected with azole resistant A. fumigatus.

Conditions

Invasive Aspergillosis

Keywords

invasive aspergillosis; PCR

Outcome Measures

Primary Outcomes (3)

• Performance of two different PCR test

  The sensitivity and specificity will be determined of the different PCR's tested including the commercially available AsperGenius (Pathonostics, Maastricht) and the in-house PCR. For this purpose a patients diagnosed with proven or probable IPA according to the EORTC/MSG definition will be used as the gold standard.

  1 week

• Performance of two different media for the PCR test

  Extraction medium (serum versus plasma) and extraction volume (1, 3 or 10 ml) that results in best sensitivity and specificity will be determined

  1 week

• Determination of best PCR cycle threshold

  Extraction medium (serum versus plasma) and extraction volume (1, 3 or 10 ml) that results in best sensitivity and specificity will be determined

  1 week

Interventions

Aspergillus PCR DIAGNOSTIC_TEST

Aspergillus PCR will be performed on different volumes of serum and plasma of patients with hematological malignancies with suspicion for invasive fungal infection.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

100 haematology patients with a radiologically suspected invasive pulmonary aspergillosis and undergoing a bronchoalveolar lavage. After the BAL diagnostic tests have become available, confirmation of the suspected infection is expected in 25 patients and therefore 25 evaluable patients will remain. The investigators decided that another 50 patients should be included because only 25% had an invasive fungal infection after interim analysis of the first 50 patients included.

You may qualify if:

• years or older.
• Lung CT shows lesions that fulfil the EORTC/MSG radiological criteria of possible invasive fungal infection.
• A bronchoalveolar lavage is planned or has been performed \<48hrs earlier

You may not qualify if:

• \- Patients unable or unwilling to provide consent

Sponsors & Collaborators

• Bart Rijnders: lead

Study Sites (1)

Erasmus Medical Center (EMC)

Rotterdam, South Holland, 3000 CA, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

80 ml of blood will be stored to analyze DNA extraction for PCR on serum and on plasma

Central Study Contacts

Bart Rijnders, MD, PhD

CONTACT

+31107033510; b.rijnders@erasmusmc.nl

Hanne Lamberink, MD

CONTACT

h.lamberink@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor in Infectious Diseases

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 5, 2023
• Study Start: July 1, 2017
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 7, 2024

Record last verified: 2024-05

Locations

NL (1)