Clinical trial NCT01176071: Correlation Between Circulating Galactomannan and Beta-D-glucan and Clinical Outcome of Invasive Aspergillosis
Official title: An Observational Assessment of the Correlation Between Circulating Galactomannan and Beta-D-glucan and Clinical Outcome in the Setting of Invasive Aspergillosis in Patients With an Underlying Hematological Disorder
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Invasive Aspergillosis
Keywords: galactomannan
beta-D-glucan
aspergillosis
outcome
Lead sponsor: University Hospital, Gasthuisberg
Sponsor class: OTHER
First posted: 2010-08-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: hematology patients with proven or probable invasive aspergillosis

Brief summary: The investigators hypothesize that early galactomannan and beta-D-glucan features, namely the height of the initial value at the time of diagnosis and the subsequent rate of marker decay within the first week(s) following therapy (day 7, day 14) are important factors in predicting clinical outcome.

Detailed description: A major challenge in the development of antifungal therapies for invasive fungal infections is the difficulty in assessing early treatment response and clinical prognosis. Mycological endpoints are often unreliable, reflected by the low sensitivity of fungal cultures to diagnose infection (20% for aspergillosis). Radiographic endpoints can be misleading, particularly when assessed early following treatment initiation. Clinical endpoints can be ambiguous indicators of treatment response, and generally include categorization of patient outcome as better, stable or worse. Furthermore, clinical assessments are likely confounded by the underlying diseases predisposing to fungal infection. Thus, a biomarker interposed between the initiation of antifungal therapy and patient outcome would bring much needed precision in the evaluation of novel antifungal drugs and thus serve as a valuable tool to guide decision-taking regarding ineffective treatments and dose selection in product development. The current absence of such biomarkers represents a critical capability gap. To date, only few studies have examined the prognostic value of fungal biomarkers in invasive aspergillosis on clinical outcome and have been limited by sample seize. To address this issue, the current study will examine the correlation between the fungal biomarkers galactomannan and beta-D-glucan with clinical outcome in invasive aspergillosis. The study will also incorporate C-reactive protein (CRP) levels, as they seem to be a useful surrogate marker of IL-6 production.

The investigator contains a sample database of 100+ patients with either probable or proven invasive aspergillosis for which daily marker levels and CRP (during the first two weeks of antifungal therapy) were measured and clinical assessment data at (2, 4 and ) 6 weeks post-treatment.

The study will evaluate whether serial serum measurements of galactomannan/beta-D-glucan during the first week(s) of antifungal therapy can distinguish between successful clinical outcome and failed clinical outcome at 6 weeks in patients with proven and probable invasive aspergillosis.

The study aims also at exploring various cut points for galactomannan/beta-D-glucan measurements at two weeks after initiation of antifungal therapy and at exploring the sensitivity and specificity for predicting clinical outcome at 6 and 12 weeks in patients with proven and probable invasive aspergillosis.

Eligibility criteria: Inclusion Criteria:

* proven or probable invasive aspergillosis with positive GM antigen test

Exclusion Criteria:

* Seronegative aspergillosis

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UZ Gasthuisberg Leuven
name: Johan A Maertens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: