Bronchoalveolar Lavage Lateral-Flow Device Test for Invasive Pulmonary Aspergillosis: a Multicenter Study

NCT02058316 | Completed

• 1 other identifier: 25-221
• Study Type: observational
• Target: 350
• Locations: 2 countries
• Sites: 4

Brief Summary

Background Invasive pulmonary aspergillosis (IPA) remains an important cause of morbidity and mortality among patients with hemato-oncological malignancies. Due to the crude mortality of \>90% in absence of adequate treatment, timely diagnosis and early start of antifungal therapy are key factors in the successful treatment of IPA. Various studies have shown that early initiation of antifungal therapy may improve IPA survival to above 70%. Diagnosis of IPA, however, remains difficult as clinical signs and symptoms as well as radiological findings are often unspecific and conventional culture methods lack sensitivity. In recent years antigen testing has therefore become one of the cornerstones of IPA diagnostics. Brochoalveolar lavage (BAL) Galactomannan (GM) testing is currently the most promising approach for early detection of pulmonary infections by this fungus. However, limitations of GM detection are assay turn-around time, which varies widely between centers (less than a day to several days), and the need for appropriately equipped laboratories that routinely test for this antigen. These limitations are overcome by the Aspergillus Lateral-Flow Device (LFD), a novel point-of-care (POC) test for IPA diagnosis developed by Dr Thornton at the University of Exeter, UK. This simple, rapid (15 min), single-use test can be performed in rudimentary facilities using BAL specimens. In a retrospective single centre study we have recently evaluated the LFD test in 39 BAL samples from hematologic malignancy patients and solid organ transplant recipients. Sensitivities and specificities of BAL LFD tests for probable IPA were 100% and 81%, respectively. Galactomannan levels in cases with negative LFD were significantly lower than in patients with positive LFD (P \<0.0001). We concluded that the LFD test of BAL specimens is performed easily and provides accurate and rapidly available results. Therefore, this new point-of-care test may be a very promising diagnostic approach for detecting IPA in BAL specimens from haematological malignancy and SOT patients. For routine clinical use, however, multicenter studies with larger sample sizes also from other patient collectives are necessary. In this multicenter study we will evaluate the LFD test in BAL samples. Study Objectives Primary Objectives To evaluate the Lateral Flow Device test, a rapid (15 min), point-of-care test for IPA diagnosis using bronchoalveolar lavage (BAL) fluids from patients at risk for IPA. Secondary Objective To evaluate the potential of BAL Lateral Flow Device test for prognosis in patients with IPA. Study Design This is a prospective multi-center study conducted in three centers in Austria (Graz, Vienna and Innsbruck) and one centre in Germany (Mannheim). In order to meet the objectives an estimated number of 300 BAL samples from patients at risk for IPA (50 to 100 per centre) will be included in the study cohort. The Lateral Flow Device test will be performed prospectively in BAL samples from the patients and results will be compared to GM results, PCR findings, clinical/radiological findings as well as conventional culture results. In addition, retrospective testing of BAL samples that were previously routinely tested for GM will be performed in up to three participating centers (Graz, Innsbruck and Mannheim) to ensure to reach the proposed number of 300 BAL samples. The treating clinicians will not be informed about BAL Lateral Flow Device test results and the test will therefore have no impact on patient management / treatment decisions.

Conditions

Invasive Pulmonary Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Performance of the Lateral Flow Device Test for diagnosisng of invasive pulmonary aspergillosis in BAL fluids

  BAL fluid s of included patients will be tested with the LFD. Results will be compared to other diagnostics.

  Day 1

Study Arms (1)

Patients at risk for IPA

Device: Lateral Flow Device Test

Interventions

Lateral Flow Device Test DEVICE

Testing of leftover BAL samples from clinical routine by the lateral flow device test

Patients at risk for IPA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All stored or routinely obtained BAL samples from adult patients at risk for invasive pulmonary Aspergillosis will be eligible for study inclusion. The treating clinicians will be blinded to BAL Lateral Flow Device test results and the test will therefore have no impact on patient management / treatment decisions. The treating clinicians will be blinded to BAL Lateral Flow Device test results. Test results will therefore have no impact on clinical / treatment decisions and therefore not affect the included patients. Underlying diseases, EORTC status of IFI (both available from the clinical order accompanying the BAL sample) and other microbiological/mycological test results will be recorded in an electronic data base. No patient related personal data will be required.

You may qualify if:

• a.) Patients above 18 years of age. b.) BAL sample obtained in clinical routine. c.) At risk for IFI (according to attending clinicians). Risk factors may include:
• febrile neutropenia
• induction chemotherapy
• allogeneic stem cell transplant/graft versus host disease
• clinical/radiological/mycological findings suspicious for IFI
• Solid Organ transplantation
• ICU patient
• Liver cirrhosis

You may not qualify if:

• a.) Under 18 years of age. b.) No BAL sample obtained in clinical routine. d.) Not at risk for IFI.

Sponsors & Collaborators

• Medical University of Graz: lead
• Medical University of Vienna: collaborator
• Medical University Innsbruck: collaborator
• Universitätsmedizin Mannheim: collaborator

Study Sites (4)

Medical university of Graz

Graz, Austria

Location

Innsbruck medical University

Innsbruck, Austria

Location

Medical University of Vienna

Vienna, Austria

Location

University Hospital Mannheim

Mannheim, Germany

Location

Related Publications (2)

• Eigl S, Prattes J, Lackner M, Willinger B, Spiess B, Reinwald M, Selitsch B, Meilinger M, Neumeister P, Reischies F, Wolfler A, Raggam RB, Flick H, Eschertzhuber S, Krause R, Buchheidt D, Thornton CR, Lass-Florl C, Hoenigl M. Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients. Crit Care. 2015 Apr 17;19(1):178. doi: 10.1186/s13054-015-0905-x.

  PMID: 25927915 DERIVED

• Prattes J, Flick H, Pruller F, Koidl C, Raggam RB, Palfner M, Eigl S, Buzina W, Zollner-Schwetz I, Thornton CR, Krause R, Hoenigl M. Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases. Am J Respir Crit Care Med. 2014 Oct 15;190(8):922-9. doi: 10.1164/rccm.201407-1275OC.

  PMID: 25203869 DERIVED

MeSH Terms

Conditions

Invasive Pulmonary Aspergillosis

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ. Prof.

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: February 10, 2014
• Study Start: February 1, 2013
• Primary Completion: January 1, 2019
• Study Completion: February 1, 2019
• Last Updated: September 23, 2021

Record last verified: 2021-09

Locations

AU (3); DE (1)