BIOPIC: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric Candidemia (BIOPIC)

Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric

The purpose of the study is to 1) define the operating characteristics of fungal biomarker assays in pediatric patients at high-risk for developing invasive candidiasis, 2) determine the change in fungal biomarker assay results in children who develop invasive candidiasis, and 3) create a biobank of blood samples from pediatric patients at high-risk for invasive candidiasis and those with invasive candidiasis for future testing of fungal biomarker assays and development of new fungal biomarker assays. The study will assemble a prospective cohort of pediatric patients at high-risk for developing invasive candidiasis. Blood samples for biomarker testing will be obtained at the time a patient has a clinical indication for blood culture attainment. Additional blood sampling will be performed on the sub-set of patients that are found to have invasive candidiasis. The sensitivity, specificity, PPV, and NPV of biomarker assays will be determined for each biomarker assay. No PHI will be stored in the database and limits on blood draws (3 ml/kg in an 8 week period) will be adhered to.

Study Overview

• Status: Completed
• Conditions: Invasive Candidiasis

Detailed Description

This study will create an international multi-center cohort of children with new clinical concern for infection while in the hospital. Sites used are part of the International Pediatric Fungal Network (ipfn.org). The study plans to prospectively enroll pediatric patients at high-risk of developing invasive candidiasis over a four year period. The study duration per subject will be up to 14 days for blood collection and 30 days for data collection from the medical record.

For the first aim, this study will assemble a prospective cohort of pediatric patients at high-risk for developing invasive candidiasis. Blood samples for biomarker testing will be obtained within 24-hours of a patient having a clinical indication for blood culture attainment. To accomplish the second aim, additional blood sampling will be performed in the sub-set of patients that are found to have invasive candidiasis. For the third aim, remnant blood samples following biomarker testing from all consenting participants will be stored in a biobank. This biobank will be used to examine future, currently undeveloped, biomarker assays in an effort to further reduce the time to diagnosis of invasive candidiasis.

• Study Type: Observational
• Enrollment (Actual): 515

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece
    • 3rd Department Pediatrics Aristole University School of Medicine, Hippokration Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital and Research Center
• Spain
  • Barcelona, Spain
    • Hospital d'Unverisitari Vall d'Hebron
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States
      • Children's Hospital of Orange County
    • San Diego, California, United States
      • Rady Children's Hospital
    • San Francisco, California, United States
      • UCSF Benioff Children's Hospital
  • Florida
    • Saint Petersburg, Florida, United States
      • All Children's Hospital
  • Illinois
    • Chicago, Illinois, United States
      • Ann and Robert Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States
      • Children's Mercy
  • New York
    • New Hyde Park, New York, United States
      • Cohen Children's Medical Center of New York
    • New York, New York, United States
      • New York-Presbyterian Phyllis and David Komansky Center for Children's Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States
      • Cleveland Clinic Children's
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States
      • Children's Hospital of Pittsburgh
  • Tennessee
    • Memphis, Tennessee, United States
      • St Jude Children's Research Hospital
  • Texas
    • Austin, Texas, United States
      • Dell Children's Medical Center
    • Houston, Texas, United States
      • Texas Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will create an international multi-center cohort of children with new clinical concern for infection while in the hospital.

Description

Inclusion Criteria:

1. Males or females age > 120 days and <18 years

2. Have at least one of the following conditions:

   • admitted to a non-neonatal ICU with any underlying disease
   • being transferred imminently to a non-neonatal ICU with any underlying disease
   • have gastro-intestinal insufficiency (eg. chronic short-gut syndrome) and admitted to anywhere in the hospital
   • have a hematological malignancy (limited to AML, ALL, non-Hodgkin's lymphoma and myelodysplastic syndrome) and admitted to anywhere to the hospital
   • have a solid tumor malignancy and admitted to anywhere in the hospital
   • have a solid organ transplant and be admitted to anywhere in the hospital
   • have a hemopoietic stem cell or bone marrow transplant and be admitted to anywhere in the hospital
   • have aplastic anemia and be admitted to anywhere in the hospital
3. Have ≥ 1 central catheter (arterial or venous)
4. Have ≥ 1 blood culture drawn for clinical concern of infection at time of enrollment
5. Clinician initiates and/or changes any systemic antimicrobial therapy at time of enrollment
6. Parental/guardian permission (informed consent) and, if appropriate, child assent.
7. For Aim 2: Each of the above AND a positive blood culture or sterile site culture for Candida spp. that turns positive between day 0 and day +14.

Exclusion Criteria:

1. Diagnosis of an invasive fungal disease within the 30 days prior to the blood culture drawn of clinical concern of infection.
2. Previous inclusion in this study
3. Weight < 4 kg (Due to constraints of no more than 3 ml/kg of blood to be drawn over an 8 week period). Subjects that fall below 4 kg during the study period that blood draws are occurring will not have more than 0.75 ml/kg of blood drawn each time.
4. Patient receiving empiric anti-fungal therapy for prolonged neutropenia or fever that was started prior to the time of blood culture
5. If blood cultures obtained and anti-infectives are added/changed only as part of a local protocol and not dictated by clinical concern of infection

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NPV, PPV, sensitivity, specificity, and threshold for positive result of fungal biomarker assays	Operating characteristics of fungal biomarker assays in pediatric patients at high-risk for developing invasive candidiasis	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in fungal biomarker assay results	Measure the change in fungal biomarker assay results in those children who developed invasive candidiasis in order to monitor their response to therapy	14 days

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Brian T Fisher, DO, MPH, MSCE, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Fisher BT, Boge CLK, Xiao R, Shuster S, Chin-Quee D, Allen J, Shaheen S, Hayden R, Suganda S, Zaoutis TE, Chang YC, Yin DE, Huppler AR, Danziger-Isakov L, Muller WJ, Roilides E, Romero J, Sue PK, Berman D, Wattier RL, Halasa N, Pong A, Maron G, Soler-Palacin P, Hutto SC, Gonzalez BE, Salvatore CM, Rajan S, Green M, Doby Knackstedt E, Hauger SB, Steinbach WJ. Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents. Clin Infect Dis. 2022 Aug 25;75(2):248-259. doi: 10.1093/cid/ciab928.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ACTUAL): October 8, 2020
• Study Completion (ACTUAL): October 8, 2020

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 19, 2014
• First Posted (ESTIMATE): August 20, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 10, 2022
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric; Candida; Fungal; IPFN; Biomarker Assays; Pediatric ICU patient
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Candidiasis; Candidiasis, Invasive
• Other Study ID Numbers: Pro00056090