Comparison of Uncomplicated Candidemia Therapy Duration in Children (COUNT)

Arkansas Children's Hospital Research Institute

Status: Enrolling

Conditions: Invasive Candidiasis

Treatments: Other: therapy duration

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05763251

1R01AI170385-01 (U.S. NIH Grant/Contract)

22-020057

Details and patient eligibility

About

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.

Full 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.

Enrollment: 420 estimated patients

Sex: All

Ages: 120 days to 18 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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420 participants in 2 patient groups

Short-course therapy

Experimental group

Description:

pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy will receive no additional antifungal therapy

Treatment:

Other: therapy duration

Standard-course therapy

No Intervention group

Description:

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