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

NCT ID: NCT02220790

Last Updated: 2022-02-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 515 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2020-10-08

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.

Conditions

Invasive Candidiasis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

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

• Minimum Eligible Age: 120 Days
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William J Steinbach, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Brian T Fisher, DO, MPH, MSCE

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital of Orange County

Orange, California, United States

Rady Children's Hospital

San Diego, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

All Children's Hospital

St. Petersburg, Florida, United States

Ann and Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Mercy

Kansas City, Missouri, United States

Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

New York-Presbyterian Phyllis and David Komansky Center for Children's Health

New York, New York, United States

Duke University

Durham, North Carolina, United States

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Children's

Cleveland, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Dell Children's Medical Center

Austin, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

3rd Department Pediatrics Aristole University School of Medicine, Hippokration Hospital

Thessaloniki, , Greece

King Faisal Specialist Hospital and Research Center

Riyadh, , Saudi Arabia

Hospital d'Unverisitari Vall d'Hebron

Barcelona, , Spain

Countries

United States; Greece; Saudi Arabia; Spain

References

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.

Reference Type: RESULT

PMID: 35134165 (View on PubMed)

Other Identifiers

Pro00056090

Identifier Type: -

Identifier Source: org_study_id