Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections (DOMINIC)

This study will establish a non-invasive diagnostic approach and evaluate clinical outcomes for children at high-risk for pulmonary invasive fungal infection (PIFI).

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Invasive Fungal Infections; Pulmonary Invasive Aspergillosis
• Intervention / Treatment: Diagnostic test: Non-Invasive Testing for PIFI

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: PFN Central Coordinator; Phone Number: 501-364-3057; Email: PFNClinical@uams.edu

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E8
      • Recruiting
      • The Hospital for Sick Children
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Research Institute
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • Rady Children's Hospital, UCSD
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Lucile Packard Children's Hospital, Stanford University
    • San Francisco, California, United States, 94143
      • Withdrawn
      • University of California San Francisco, Benioff Children's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2916
      • Recruiting
      • Children's National Hospital
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Active, not recruiting
      • All Children's Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University-Children's Healthcare of Atlanta (CHOA)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medicine, Comer Children's
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02241
      • Recruiting
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Active, not recruiting
      • University of Minnesota Medical School
    • Saint Paul, Minnesota, United States, 55102
      • Recruiting
      • Children's Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Children's Mercy
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • The Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Recruiting
      • Children's Omaha
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Weil Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Active, not recruiting
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Withdrawn
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43205-2664
      • Recruiting
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Recruiting
      • The Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Ascension Seton Medical Center
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwest Medical Center (UTSW)
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Research Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients receiving care at a participating study site

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with possible PIFI	Diagnostic test: Non-Invasive Testing for PIFI; galactomannan assay, fungal PCRs, cell-free next-generation DNA/RNA sequencing, RNAseq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Likelihood ratio of molecular RNAseq platform assessing host immune response to return a negative result among subjects determined not to have PIFI	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome score between patients with possible pulmonary invasive fungal infection managed with empirical antifungal therapy versus an invasive diagnostic procedure	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)	49 days

Collaborators and Investigators

• Sponsor: Arkansas Children's Hospital Research Institute
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Brian Fisher, Children's Hospital of Philadelphia; Principal Investigator: William Steinbach, University of Arkansas

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections and Mycoses; Lung Diseases, Fungal; Pulmonary Aspergillosis; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Aspergillosis; Invasive Pulmonary Aspergillosis
• Other Study ID Numbers: Pro00094558; R01AI139032 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No