Clinical trial NCT05763251: Comparison of Uncomplicated Candidemia Therapy Duration in Children
Official title: Short Course Versus Standard Course Antifungal Therapy for Uncomplicated Candidemia in Children and Adolescents: A Multi-Center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Invasive Candidiasis
Lead sponsor: Arkansas Children's Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Westat
name: St. Jude Children's Research Hospital
name: George Washington University
name: Children's Hospital of Philadelphia
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2023-03-10
Enrollment: 420
Sex: ALL
Minimum age (years): 120
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age \> 120 days and \< 18 years at the time of positive 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 or anidulafungin) 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. from repeat blood culture(s) obtained on or before day of randomization;
5. Partial or complete clinical response, as defined by published guidelines, on or before day of randomization;
6. No evidence of metastatic foci of infection at the time of randomization, as documented by a negative abdominal ultrasound or abdominal CT scan of the liver, spleen, and kidneys and negative ophthalmologic examination.

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)

Primary outcomes:
measure: Compare the desirability of outcome ranking (DOOR) in short-course vs standard-course arm
timeFrame: The measures assigned on Day 14 will inform the primary analysis for the primary objective
Secondary outcomes:
measure: Compare the DOOR for subjects with a negative vs positive T2 Candida® biomarker at day 7
timeFrame: The DOOR measure on Day 14 will be used for the primary analysis for the secondary objective.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
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: New Haven
country: United States
facility: Yale New Haven Children's Hospital
state: Connecticut
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Comer Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Brian Fisher, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Arkansas Children's Hospital Research Institute
name: William J Steinbach, MD
role: PRINCIPAL_INVESTIGATOR
References: