Diagnostic Study of Combined Biomnarker Testing in Bronchoalveolar Lavage Samples of Immunocompromised Patients

NCT01695512 | Unknown

• 2 other identifiers: University of HeidelbergGrant Funding number
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of our prospective and multicentre diagnostic study is therefore to elucidate on the sensitivity and specificity rates of these serologic markers in combination with molecular tools (both an Aspergillus specific and a multifungal PCR based assay), as serologic mark-ers are not pathogen-specific, and furthermore to define species-specific cut-off values for BDG in BAL samples. Additionally, if genomic material of Aspergillus fumigatus is detected by PCR in a clinical sample, we investigate fungal DNA for point mutations in the cyp51A gene mediating resis-tance against common mould-active triazoles with novel rapid, sensitive and specific, non-culture-based PCR-assays and sequencing to optimize antifungal treatment as early as pos-sible.

Conditions

Invasive Aspergillosis; Acute Leukemia; Biomarkers; Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Diagnostic certainty

  After 6 weeks the diagnostic performance of the biomarkers and their combination in relation to diagnostic accuracy will be measured

  6 Weeks

Study Arms (2)

Immunocompromised Patients

Patients with acute leukemia undergoing induction chemotherapy or undergoing allogeneic stem cell transplantation

Control Group

Patients underdoing bronchoscopy and diagnostic BAL without immunosuppression and without signs of infection (Sarcoidosis, Lung Cancer)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients suffering from acute leukemia and pts after allogeneic stem cell transplantation with febrile neutropenia and lung infiltrates diagnosed in a chest CT scan suggestive for fungal infection will be investigated after pts's informed consent in a multicentre, prospective trial

You may qualify if:

• acute leukemia or after allogeneic stem cell transplantation
• febrile neutropenia
• lung infiltrates suggestive for fungal infection (halo sign. nodules, air-crescent sign)

You may not qualify if:

• missing informed consent
• other underlying diagnosis

Sponsors & Collaborators

• Heidelberg University: lead
• Gilead Sciences: collaborator

Study Sites (1)

University Hospital Mannheim

Mannheim, 68167, Germany

Location

Related Publications (4)

• Reinwald M, Hummel M, Kovalevskaya E, Spiess B, Heinz WJ, Vehreschild JJ, Schultheis B, Krause SW, Claus B, Suedhoff T, Schwerdtfeger R, Reuter S, Kiehl MG, Hofmann WK, Buchheidt D. Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies. J Antimicrob Chemother. 2012 Sep;67(9):2260-7. doi: 10.1093/jac/dks208. Epub 2012 Jun 27.

  PMID: 22740590 BACKGROUND

• Reinwald M, Spiess B, Heinz WJ, Vehreschild JJ, Lass-Florl C, Kiehl M, Schultheis B, Krause SW, Wolf HH, Bertz H, Maschmeyer G, Hofmann WK, Buchheidt D. Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples. Eur J Haematol. 2012 Aug;89(2):120-7. doi: 10.1111/j.1600-0609.2012.01806.x. Epub 2012 Jun 22.

  PMID: 22650156 BACKGROUND

• Spiess B, Seifarth W, Merker N, Howard SJ, Reinwald M, Dietz A, Hofmann WK, Buchheidt D. Development of novel PCR assays to detect azole resistance-mediating mutations of the Aspergillus fumigatus cyp51A gene in primary clinical samples from neutropenic patients. Antimicrob Agents Chemother. 2012 Jul;56(7):3905-10. doi: 10.1128/AAC.05902-11. Epub 2012 Apr 23.

  PMID: 22526309 BACKGROUND

• Spiess B, Postina P, Reinwald M, Cornely OA, Hamprecht A, Hoenigl M, Lass-Florl C, Rath PM, Steinmann J, Miethke T, Lauten M, Will S, Merker N, Hofmann WK, Buchheidt D. Incidence of Cyp51 A key mutations in Aspergillus fumigatus-a study on primary clinical samples of immunocompromised patients in the period of 1995-2013. PLoS One. 2014 Jul 29;9(7):e103113. doi: 10.1371/journal.pone.0103113. eCollection 2014.

  PMID: 25072733 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Only fungal DNA is retained and investigated

Study Officials

• Dieter Buchheidt, MD

  Medical Faculty Mannheim, University of Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. Dieter Buchheidt

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 20, 2020

Record last verified: 2020-04

Locations

DE (1)