Comparison of Uncomplicated Candidemia Therapy Duration in Children (COUNT)

Short Course Versus Standard Course Antifungal Therapy for Uncomplicated Candidemia in Children and Adolescents: A Multi-Center Randomized Controlled Trial

The goal of this clinical trial is to compare antifungal therapy duration in pediatric uncomplicated candidemia. The specific aims are:

• Compare the desirability of outcome ranking in children with uncomplicated candidemia randomized to 7 additional days of antifungal therapy (standard-course) versus no additional antifungal therapy (short-course) after already receiving 7 days of echinocandin therapy.
• Compare the 14-day desirability of outcome measure for subjects with a negative and those with a positive T2Candida® biomarker at day 7 of therapy within randomized groups.

Participants meeting eligibility criteria will be approached and consented between day 5 and 7 of primary systemic antifungal therapy. On day 7 of primary systemic antifungal therapy, inclusion and exclusion criteria will again be reviewed for consented patients and those still eligible will be randomized 1:1 to the two study arms. Researchers will compare no additional antifungal therapy (short-course) versus 7 additional days of systemic antifungal therapy (standard-course) in pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy to see if shorter durations are as effective as longer durations in treating uncomplicated candidemia.

Study Overview

• Status: Recruiting
• Conditions: Invasive Candidiasis
• Intervention / Treatment: Other: therapy duration

Detailed Description

The primary objective of this study will be addressed with a multi-center open label randomized controlled trial designed to compare no additional antifungal therapy (short-course) versus 7 additional days of systemic antifungal therapy (standard-course) in pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy. The secondary objective of this study is an embedded observational biomarker study. This objective will determine if the novel T2Candida® biomarker performed at the time of randomization (i.e. Day 7 of systemic antifungal therapy) will be associated with patient outcomes assessed at Day 14. The results of the T2Candida® biomarker will not be available in real-time and thus will not impact the primary study objective. Eligible patients will be any hospitalized patient at a participating center with uncomplicated candidemia that is older than 120 days and <18 years of age at time of candidemia onset. Patients need to receive an echinocandin as their primary antifungal therapy for at least three days and continue systemic antifungal therapy (either with an echinocandin or step-down to an azole) for a total of 7 days from their first negative blood culture and have no evidence of metastatic foci of candidemia at the time of randomization. Patients with neutropenia or anticipated to have neutropenia during the study follow-up window will not be eligible. Patients can only be enrolled to the study once. This study population will serve as the source cohort for both study objectives. Patients will be randomized 1:1 to one of two study arms, short-course therapy or standard-course therapy. Patients will be followed for 21 days from the day of randomization (Day 7 to Day 28) to capture primary and secondary outcome measures.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah K Johnson, PhD; Phone Number: 501-364-3057; Email: skjohnson@uams.edu
• Study Contact Backup: Name: Sydney Shuster, MPH; Phone Number: 267-425-1462; Email: shusters@chop.edu

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Perth Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Children's Hospital of Alabama
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale New Haven Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 31193
      • Recruiting
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Comer Children's Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • CS Mott Children's Hospital
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Syd Shuster; Phone Number: 267-425-1462; Email: shusters@chop.edu
  • Texas
    • Austin, Texas, United States, 78723
      • Recruiting
      • Dell Children's Medical Center
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • Primary Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 17 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age > 120 days at the time of the first negative blood culture at any participating site;
2. Candidemia with at least one positive blood culture for any Candida spp;
3. Receiving/received an echinocandin (caspofungin, micafungin, anidulafungin, or rezafungin) as primary antifungal therapy for candidemia for at least 2 days from day of first negative culture with continuation of uninterrupted systemic antifungal therapy at the time of enrollment);
4. Sustained clearance of Candida spp. defined as negative blood culture(s) obtained after onset of candidemia and before day of randomization;
5. Partial or complete clinical response, as defined by published guidelines (Table 5), on or before day of randomization;
6. Between the onset of qualifying candidemia and randomization, no suspicion of disseminated candidiasis by patient's clinical team or, if deemed clinically necessary, documented negative radiological imaging such as an abdominal ultrasound or abdominal CT scan.

Exclusion Criteria:

1. Already receiving antifungal therapy for a previously diagnosed systemic invasive fungal disease;
2. Neutropenic (absolute neutrophil count < 500 cells/µl) at the time of enrollment or anticipated to be neutropenic in the week following randomization;
3. Have an underlying condition that requires them to be on antifungal prophylaxis when not receiving directed therapy for an invasive fungal disease;
4. Previous enrollment in this trial;
5. Females of childbearing age with a current pregnancy diagnosis or without a negative pregnancy test for their current admission;
6. A documented DNR order;
7. Have an implantable cardiac device (e.g., ventricular assist device, pacemaker)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short-course therapy; pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy will receive no additional antifungal therapy	Other: therapy duration; the standard-course arm will receive 14 days total of antifungal therapy and the short-course arm will only receive 7 days of therapy
No Intervention: Standard-course therapy; pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy will receive 7 additional days of systemic antifungal therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the desirability of outcome ranking (DOOR) in short-course vs standard-course arm	The primary analysis for the primary objective will compare the DOOR distributions at 7 days from randomization (i.e., outcome assessment on Day 14 from first negative blood culture) between subjects from the two study groups, based on randomized treatment assignments, in accordance with the intention-to-treat principle. The primary analysis will use the DOORs assigned on this day to assess which therapy course is better, short-course or standard-course.	The measures assigned on Day 14 will inform the primary analysis for the primary objective

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the DOOR for subjects with a negative vs positive T2 Candida® biomarker at day 7	The results of the Day 7 T2Candida® biomarker (i.e. detected versus not detected) and the randomization group (i.e. short-course versus standard-course) will allow for the following four subsets of patients: 1. Patient is randomized to short-course group and has a not-detected result for the T2Candida® biomarker at time of randomization; 2. patient is randomized to short-course group and has a detected T2Candida® biomarker at time of randomization; 3. patient is randomized to standard-course group and has a not-detected result for the T2Candida® biomarker at time of randomization; 4. patient is randomized to standard-course group and has a detected T2Candida® biomarker at time of randomization. This analysis will compare the DOOR categories between the first two groups (i.e. short-course and not-detected versus short-course and detected) and then be repeated for the second two groups (i.e. standard-course and not detected versus standard-course and detected).	The DOOR measure on Day 14 will be used for the primary analysis for the secondary objective.

Collaborators and Investigators

• Sponsor: Arkansas Children's Hospital Research Institute
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Children's Hospital of Philadelphia; St. Jude Children's Research Hospital; George Washington University; Westat
• Investigators: Principal Investigator: Brian Fisher, DO, Children's Hospital of Philadelphia; Principal Investigator: William J Steinbach, MD, Arkansas Children's Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2023
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2032

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Invasive Fungal Infections; Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Candidiasis, Invasive; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Duration of Therapy
• Other Study ID Numbers: 22-020057; 1R01AI170385-01 (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
• product manufactured in and exported from the U.S.: Yes