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

Sponsor

Duke University (Other)

Overall Status

Completed

CT.gov ID

NCT02220790

Collaborator

Children's Hospital of Philadelphia (Other)

515

Enrollment

Locations

69.2

Duration (Months)

23.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

515 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Oct 8, 2020

Actual Study Completion Date :

Oct 8, 2020

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

change in fungal biomarker assay results [14 days]
Measure the change in fungal biomarker assay results in those children who developed invasive candidiasis in order to monitor their response to therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

120 Days to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females age > 120 days and <18 years
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

Have ≥ 1 central catheter (arterial or venous)
Have ≥ 1 blood culture drawn for clinical concern of infection at time of enrollment
Clinician initiates and/or changes any systemic antimicrobial therapy at time of enrollment
Parental/guardian permission (informed consent) and, if appropriate, child assent.
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:

Diagnosis of an invasive fungal disease within the 30 days prior to the blood culture drawn of clinical concern of infection.
Previous inclusion in this study
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.
Patient receiving empiric anti-fungal therapy for prolonged neutropenia or fever that was started prior to the time of blood culture
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States
2	Children's Hospital of Orange County	Orange	California	United States
3	Rady Children's Hospital	San Diego	California	United States
4	UCSF Benioff Children's Hospital	San Francisco	California	United States
5	All Children's Hospital	Saint Petersburg	Florida	United States
6	Ann and Robert Lurie Children's Hospital of Chicago	Chicago	Illinois	United States
7	Boston Children's Hospital	Boston	Massachusetts	United States
8	Children's Mercy	Kansas City	Missouri	United States
9	Cohen Children's Medical Center of New York	New Hyde Park	New York	United States
10	New York-Presbyterian Phyllis and David Komansky Center for Children's Health	New York	New York	United States
11	Duke University	Durham	North Carolina	United States	27710
12	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States
13	Cleveland Clinic Children's	Cleveland	Ohio	United States
14	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States
15	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States
16	St Jude Children's Research Hospital	Memphis	Tennessee	United States
17	Dell Children's Medical Center	Austin	Texas	United States
18	Texas Children's Hospital	Houston	Texas	United States
19	Medical College of Wisconsin	Milwaukee	Wisconsin	United States
20	3rd Department Pediatrics Aristole University School of Medicine, Hippokration Hospital	Thessaloniki		Greece
21	King Faisal Specialist Hospital and Research Center	Riyadh		Saudi Arabia
22	Hospital d'Unverisitari Vall d'Hebron	Barcelona		Spain

Sponsors and Collaborators

Duke University
Children's Hospital of Philadelphia

Investigators

Principal Investigator: William J Steinbach, MD, Duke University
Principal Investigator: Brian T Fisher, DO, MPH, MSCE, Children's Hospital of Philadelphia