Invasive Candidiasis
Conditions
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.
Interventions
OTHERtherapy 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
Sponsors
Arkansas Children's Hospital Research Institute
Westat
St. Jude Children's Research Hospital
George Washington University
Children's Hospital of Philadelphia
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
120 Days to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare the desirability of outcome ranking (DOOR) in short-course vs standard-course arm | The measures assigned on Day 14 will inform the primary analysis for the primary objective | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the DOOR for subjects with a negative vs positive T2 Candida® biomarker at day 7 | The DOOR measure on Day 14 will be used for the primary analysis for the secondary objective. | 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). |
Countries
Australia, United States
Contacts
CONTACTSarah K Johnson, PhD
CONTACTSydney Shuster, MPH
PRINCIPAL_INVESTIGATORBrian Fisher, DO
Children's Hospital of Philadelphia
PRINCIPAL_INVESTIGATORWilliam J Steinbach, MD
Arkansas Children's Hospital Research Institute
Outcome results
None listed