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Aspergillosis InvasiveNCT03004092

Novel Biomarkers for Invasive Aspergillosis

A study testing blood sample in people with Aspergillosis Invasive, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Diagnosis of invasive aspergillosis remains difficult, and is often based on a combination of patient characteristics, radiological and microbiological findings. To data, galactomannan (GM) is the only well-validated biomarker available. However, GM still has its shortcomings. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Aspergillosis Invasive
What is being tested?
blood sample
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
226 participants
Where
1 siteBelgium
Study dates
Jan 2017to Feb 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 16y at start of study
  • One of the following diagnoses:
  • De novo, refractory or relapsed AML/MDS receiving intensive chemotherapy
  • De novo, refractory or relapsed ALL/T-lymphoblastic lymphoma receiving intensive chemotherapy
  • Aplastic anemia requiring ATG therapy
  • Any patient admitted for either autologous or allogeneic hematopoietic stem cell transplantation
  • Written informed consent obtained from the patient

Who cannot join

  • AML or ALL beyond the specified inclusion criteria
  • Directed treatment for possible, probable, or proven invasive aspergillosis, at moment of screening, or with end of treatment < 6 weeks at screening, or no complete response according to EORTC/MSG criteria, or complete response achieved < 6 weeks at time of screening.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • University Hospitals Leuven

    Leuven, 3000

Other trials in Belgium

About this study

Diagnosis of invasive aspergillosis remains difficult, and is often based on a combination of patient characteristics, radiological and microbiological findings. To data, galactomannan (GM) is the only well-validated biomarker available. However, GM still has its shortcomings. There is therefore a need for new, complementary biomarkers. In this study, two of those tests, bis(methylthio)gliotoxin (bmGT) and a lateral flow device, will be validated in a hematological population, and compare it to GM.

Read the detailed description

Diagnosis of invasive aspergillosis is often difficult to achieve with certainty, as this requires direct evidence of invasive growth on histopathological examination. A probable diagnosis can be suspected based on both clinical and mycological evidence of the disease, in presence of a susceptible patient. The EORTC-MSG guidelines offer a widely accepted basis for this diagnosis. Under these guidelines, mycological evidence can consist of a positive culture of aspergillus spp, or of detection of galactomannan (GM) in a relevant body sample. GM is a part of the Aspergillus mould and can be detected using a commercially available immunoenzymatic sandwich microplate assay. However, like most biomarkers, galactomannan is far from a perfect biomarker. Several beta-lactam antibiotics are known to cause false positives, and anti-mould therapy has been reported to significantly lower the sensitivity[1]. Additional biomarkers that could circumvent these problems would therefore be beneficial.

A potential new target is gliotoxin (GT), a secondary metabolite of several fungi, the most clinically important of which is Aspergillus[2]. GT is released during invasive growth, and can therefore be used as a biomarker of invasive fungal disease by GT-producing fungi. However, GT is quickly removed by red blood cells from circulation, making it an unreliable marker[3]. A degradation product of GT, bis(methylthio)gliotoxin (bmGT), appears to be more stable as it is not taken up by red blood cells. Serum bmGT or bmGT in bronchoalveolar lavage (BAL) fluid has already been shown in small studies to be a potential marker of invasive aspergillosis, especially when used in combination with GM[3-5].

Recently, another highly specific test has become available, based on detection of an extracellular glycoprotein secreted during the growth of Aspergillus species, using a monoclonal antibody (JF5) in an immunochromatographic lateral-flow device (LFD)[6,7]. This test allows fast (<15 minutes) testing using a commercially available device.

In this study, both the LFD and bmGT will be characterized and validated in a hematological population, and compared to GM.

Being tested
blood sample
Keywords
bis(methylthio)gliotoxin, lateral flow device, JF5, Galactomannan, Invasive aspergillosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • blood sampleProcedure or surgery

    Twice weekly blood sample, and at every outpatient visit

Study groups in NCT03004092
Study groupRoleWhat they receive
Total cohortExperimentalNot described
Receives: Procedure: blood sample

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Diagnostic accuracy of serum bmGT

    Determine the diagnostic accuracy (specificity, sensitivity predictive values, accuracy and other key diagnostic values) of serum bmGT in the diagnosis of invasive aspergillosis, using the revised EORTC criteria as gold standard.

    Measured: 2 weeks

Secondary outcomes (7)

  1. Diagnostic accuracy of a combination of serum bmGT and serum GM

    Determine diagnostic accuracy of a combination of serum GM and serum bmGT in the diagnosis of invasive aspergillosis.

    Measured: 2 weeks

  2. Prognostic value of serum bmGT

    Determine prognostic value (therapy response / mortality) of initial serum bmGT levels.

    Measured: 6 weeks

  3. Prognostic value of serum bmGT kinetics

    Evaluate serum bmGT kinetics as surrogate marker of therapeutic response.

    Measured: 6 weeks

  4. Renal and hepatic influence on bmGT

    Evaluate the impact of renal and hepatic function on initial bmGT levels and bmGT kinetics.

    Measured: 2 weeks

  5. Compare bmGT-HPTLC to bmGT-LC/MS

    Compare bmGT levels as measured by HPTLC to levels as measured by our own in-house developed chromatographic method.

    Measured: Same day

  6. Diagnostic accuracy of BAL bmGT

    Determine diagnostic accuracy of bmGT in BAL in the diagnosis of invasive aspergillosis.

    Measured: 2 weeks

  7. Diagnostic accuracy of LFD

    Determine diagnostic accuracy of the lateral flow device (LFD) in BAL and serum in the diagnosis of invasive aspergillosis.

    Measured: 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2016 (estimated)
  2. Study startJan 2017
  3. Primary completionDec 2019
  4. Study completionFeb 2020

Why it stopped: The project with number S59863 has been completely transferred to S61979 - Hemoba

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
226 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03004092
Sponsor's protocol ID
S59863
Status last verified
Jul 2024
First submitted
21 Dec 2016
Last updated
3 Jul 2024
Results posted
No
Data monitoring committee
No

Publications

  • Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006 May 15;42(10):1417-27. doi: 10.1086/503427. Epub 2006 Apr 14.

    PubMed 16619154

  • Lewis RE, Wiederhold NP, Chi J, Han XY, Komanduri KV, Kontoyiannis DP, Prince RA. Detection of gliotoxin in experimental and human aspergillosis. Infect Immun. 2005 Jan;73(1):635-7. doi: 10.1128/IAI.73.1.635-637.2005.

    PubMed 15618207

  • Domingo MP, Colmenarejo C, Martinez-Lostao L, Mullbacher A, Jarne C, Revillo MJ, Delgado P, Roc L, Meis JF, Rezusta A, Pardo J, Galvez EM. Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis. Diagn Microbiol Infect Dis. 2012 May;73(1):57-64. doi: 10.1016/j.diagmicrobio.2012.01.012. Epub 2012 Apr 4.

    PubMed 22480566

  • Vidal-Garcia M, Domingo MP, De Rueda B, Roc L, Delgado MP, Revillo MJ, Pardo J, Galvez EM, Rezusta A. Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis. Appl Microbiol Biotechnol. 2016 Mar;100(5):2327-34. doi: 10.1007/s00253-015-7209-6. Epub 2015 Dec 17.

    PubMed 26678078

  • Thornton CR. Development of an immunochromatographic lateral-flow device for rapid serodiagnosis of invasive aspergillosis. Clin Vaccine Immunol. 2008 Jul;15(7):1095-105. doi: 10.1128/CVI.00068-08. Epub 2008 May 7.

    PubMed 18463222

  • Mercier T, Guldentops E, Lagrou K, Maertens J. Prospective Evaluation of the Turbidimetric beta-D-Glucan Assay and 2 Lateral Flow Assays on Serum in Invasive Aspergillosis. Clin Infect Dis. 2021 May 4;72(9):1577-1584. doi: 10.1093/cid/ciaa295.

    PubMed 32188971

Questions about this trial

What is this clinical trial studying?

A study testing blood sample in people with Aspergillosis Invasive, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: The project with number S59863 has been completely transferred to S61979 - Hemoba). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diagnostic accuracy of serum bmGT (time frame: 2 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03004092, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.

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