Clinical trial NCT02220790: BIOPIC: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric Candidemia
Official title: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Invasive Candidiasis
Keywords: IPFN
Pediatric
Fungal
Biomarker Assays
Candida
Pediatric ICU patient
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
First posted: 2014-08-20
Enrollment: 515
Sex: ALL
Minimum age (years): 120
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: NPV, PPV, sensitivity, specificity, and threshold for positive result of fungal biomarker assays
timeFrame: 1 day
Secondary outcomes:
measure: change in fungal biomarker assay results
timeFrame: 14 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann and Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy
state: Missouri
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: New York-Presbyterian Phyllis and David Komansky Center for Children's Health
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Children's
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Thessaloniki
country: Greece
facility: 3rd Department Pediatrics Aristole University School of Medicine, Hippokration Hospital
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Center
city: Barcelona
country: Spain
facility: Hospital d'Unverisitari Vall d'Hebron
Study officials:
affiliation: Duke University
name: William J Steinbach, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Brian T Fisher, DO, MPH, MSCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.