Clinical trial NCT03827694: Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections
Official title: Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pulmonary Invasive Fungal Infections
Pulmonary Invasive Aspergillosis
Lead sponsor: Arkansas Children's Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2019-02-01
Enrollment: 400
Sex: ALL
Minimum age (years): 120
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients receiving care at a participating study site

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).


Eligibility criteria: 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

Primary outcomes:
measure: Likelihood ratio of the galactomannan assay to return a positive result among subjects determined to have PIFI
timeFrame: Baseline
measure: Likelihood ratio of galactomannan assay to return a negative result among subjects determined not to have PIFI
timeFrame: Baseline
measure: Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a positive result among subjects determined to have PIFI
timeFrame: Baseline
measure: Likelihood ratio of fungal PCRs (Aspergillus PCR, Mucorales PCR) to return a negative result among subjects determined not to have PIFI
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: Likelihood ratio of molecular RNAseq platform assessing host immune response to return a positive result among subjects determined to have PIFI
timeFrame: Baseline
measure: Likelihood ratio of molecular RNAseq platform assessing host immune response to return a negative result among subjects determined not to have PIFI
timeFrame: Baseline
Secondary outcomes:
measure: Composite outcome score between patients with possible pulmonary invasive fungal infection managed with empirical antifungal therapy versus an invasive diagnostic procedure
timeFrame: 49 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Research Institute
state: Arkansas
city: La Jolla
country: United States
facility: Rady Children's Hospital, UCSD
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital, Stanford University
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Benioff Children's Hospital
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Saint Petersburg
country: United States
facility: All Children's Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University-Children's Healthcare of Atlanta (CHOA)
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine, Comer Children's
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Saint Paul
country: United States
facility: Children's Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy
state: Missouri
city: Saint Louis
country: United States
facility: The Washington University
state: Missouri
city: Omaha
country: United States
facility: Children's Omaha
state: Nebraska
city: New York
country: United States
facility: Weil Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Ascension Seton Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwest Medical Center (UTSW)
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: University of Arkansas
name: William Steinbach
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Brian Fisher
role: PRINCIPAL_INVESTIGATOR
References: