Pulmonary Invasive Aspergillosis, Pulmonary Invasive Fungal Infections
Conditions
Brief summary
This study will establish a non-invasive diagnostic approach and evaluate clinical outcomes for children at high-risk for pulmonary invasive fungal infection (PIFI).
Interventions
DIAGNOSTIC_TESTNon-Invasive Testing for PIFI
galactomannan assay, fungal PCRs, cell-free next-generation DNA/RNA sequencing, RNAseq
Sponsors
Children's Hospital of Philadelphia
National Institute of Allergy and Infectious Diseases (NIAID)
Arkansas Children's Hospital Research Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
120 Days to 21 Years
Healthy volunteers
No
Inclusion criteria
* Males or females age \> 120 days and \< 22 years at any participating site * Have at least one of the following conditions associated with a known high incidence of IFI: hematopoietic stem cell transplantation (HSCT), aplastic anemia, bone marrow failure, primary or acquired immune deficiency, or malignancy * New (last 96 hours) radiographic evidence of at least one of the following: at least one nodular lesion greater than or equal to 5 mm in size, a wedge-shaped and segmental or lobar consolidation, a cavitary lesion, a lesion with a halo sign, a lesion with a reverse halo sign, or a lesion with an air crescent sign * Prolonged neutropenia (absolute neutrophil count \< 500 cells/µl for a period of ≥ 5 consecutive days) in 30 days prior to and including the day of qualifying chest MRI or CT scan date OR currently receiving systemic therapy for acute or chronic graft-versus-host disease (GVHD) OR presence of neutrophil dysfunction because of underlying acquired or primary immune deficiency (e.g. chronic granulomatous disease) on the date of the qualifying chest MRI or CT scan * Subject consent or parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion criteria
* Weight \<3 kg, so as to not exceed 3 ml/kg in a single blood draw * Previous inclusion in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Likelihood ratio of molecular RNAseq platform assessing host immune response to return a negative result among subjects determined not to have PIFI | Baseline |
| Likelihood ratio of the galactomannan assay to return a positive result among subjects determined to have PIFI | Baseline |
| Likelihood ratio of galactomannan assay to return a negative result among subjects determined not to have PIFI | Baseline |
| Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a positive result among subjects determined to have PIFI | Baseline |
| Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a negative result among subjects determined not to have PIFI | Baseline |
| Likelihood ratio of cell-free next generation DNA/RNA sequencing identifying a fungal pathogen to return a positive result among subjects determined to have PIFI | Baseline |
| Likelihood ratio of cell-free next generation DNA/RNA sequencing identifying a fungal pathogen to return a negative result among subjects determined not to have PIFI | Baseline |
| Likelihood ratio of molecular RNAseq platform assessing host immune response to return a positive result among subjects determined to have PIFI | Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite outcome score between patients with possible pulmonary invasive fungal infection managed with empirical antifungal therapy versus an invasive diagnostic procedure | 49 days | Outcome score inclusive of outcomes and adverse events. Comprehensive clinical outcome score from most to least desirable are score of 1 (survival, improvement in pulmonary nodules, no adverse events related to anti-fungal therapy or invasive diagnostic intervention) to score of 7 (death) |
Countries
Canada, United States
Contacts
Primary ContactPFN Central Coordinator
Outcome results
None listed