Antifungal Therapy Duration for Candidemia in Children

(COUNT Trial)

Recruiting at 17 trial locations

Overseen By Sydney Shuster, MPH

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Arkansas Children's Hospital Research Institute

Must be taking: Echinocandins

Disqualifiers: Neutropenia, Pregnancy, Antifungal prophylaxis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal length of antifungal treatment for children with uncomplicated candidemia, a blood infection caused by the Candida fungus. Researchers compare two treatment durations: one group receives an additional 7 days of antifungal therapy, while the other stops after the initial 7 days. The goal is to determine if a shorter treatment is as effective as a longer one. Children who have cleared a Candida blood infection after at least 7 days of treatment and show no signs of the infection spreading may qualify for this study. As an unphased trial, this study offers a unique opportunity to contribute to research that could simplify and improve treatment for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It mainly focuses on the duration of antifungal therapy for candidemia in children.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that short-term antifungal treatment for simple yeast infections in children is generally safe. In one study, only 5% of children experienced side effects, indicating that fluconazole, a common antifungal drug, is usually well-tolerated. The most common side effects were mild, such as liver and stomach issues, but these were rare.

Another study found that short-term treatment was as effective as longer treatments, but with fewer side effects. This suggests that a shorter treatment might be just as effective for children without adding extra risk.

Overall, evidence suggests that short-term antifungal treatment is generally safe for children with simple yeast infections. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether a shorter duration of antifungal therapy could be just as effective for treating candidemia in children. Currently, standard treatment involves extending antifungal therapy beyond the initial treatment period. This trial investigates if stopping treatment after just 7 days, instead of continuing for an additional week, could be sufficient for uncomplicated cases. If successful, this approach could reduce medication exposure, potential side effects, and healthcare costs, while still effectively managing the infection.

What evidence suggests that this trial's treatments could be effective for candidemia in children?

This trial will compare the effectiveness of different antifungal therapy durations for pediatric patients with uncomplicated candidemia. Research suggests that shorter antifungal treatment might be as effective as longer treatment for simple yeast infections in children. Participants in the "Short-course therapy" arm will receive no additional antifungal therapy after the initial 7 days, while those in the "Standard-course therapy" arm will receive 7 more days of systemic antifungal therapy. Studies have shown that extending treatment beyond the first 7 days doesn't necessarily improve outcomes. This suggests stopping treatment after 7 days could be as effective as continuing for 14 days. The aim is to identify the shortest effective treatment, potentially reducing side effects and easing recovery for children. Ongoing research seeks to confirm these findings and ensure that shorter treatments are safe and effective. ^{2 3 6 7 8}

Who Is on the Research Team?

Brian Fisher, DO

Principal Investigator

Children's Hospital of Philadelphia

William J Steinbach, MD

Principal Investigator

Arkansas Children's Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for children older than 120 days and younger than 18 years with a specific yeast infection in the blood, who've had successful initial treatment. They must not have other severe infections or conditions that require ongoing antifungal drugs, and girls of childbearing age must not be pregnant.

Inclusion Criteria

Candidemia with at least one positive blood culture for any Candida spp

Sustained clearance of Candida spp. from repeat blood culture(s) obtained on or before day of randomization

I have been on echinocandin antifungal treatment for candidemia for at least 3 days.

Exclusion Criteria

Previous enrollment in this trial

I need antifungal medication due to an underlying condition.

Neutropenic (absolute neutrophil count < 500 cells/μl) at the time of enrollment or anticipated to be neutropenic in the week following randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 days

1 visit (in-person)

Initial Treatment

Participants receive 7 days of primary systemic antifungal therapy

7 days

Randomization and Treatment

Participants are randomized to either receive no additional antifungal therapy (short-course) or 7 additional days of systemic antifungal therapy (standard-course)

7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 days

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• therapy duration

Trial Overview Researchers are testing if treating pediatric patients with uncomplicated candidemia for an additional 7 days after an initial week of therapy is better or equal to stopping treatment. The study randomly assigns participants to either continue or stop therapy after the first week.

How Is the Trial Designed?

Group I: Short-course therapy Experimental Treatment 1 Intervention

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

Group II: Standard-course therapy Active Control 1 Intervention

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

therapy duration is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Diflucan for:

• Candidemia
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Vaginal candidiasis

Approved in United States as Diflucan for:

• Candidemia
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Vaginal candidiasis
• Cryptococcal meningitis

Approved in Canada as Diflucan for:

• Candidemia
• Oropharyngeal candidiasis
• Esophageal candidiasis
• Vaginal candidiasis

Who Is Running the Clinical Trial?

Arkansas Children's Hospital Research Institute

Lead Sponsor

Trials

141

Recruited

5,025,000+

George Washington University

Collaborator

Trials

263

Recruited

476,000+

St. Jude Children's Research Hospital

Collaborator

Trials

451

Recruited

5,326,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Westat

Collaborator

Trials

49

Recruited

39,700+

Published Research Related to This Trial

In a study of 40 neonates and infants with fungal infections, fluconazole demonstrated a high efficacy rate, with a positive clinical response in 97% of patients and successful eradication of the fungal organism in 97% of evaluable cases.

The treatment was well-tolerated, with only 5% of patients experiencing adverse events, indicating that fluconazole is a safe and effective option for young patients when conventional antifungal therapies are not suitable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluconazole treatment of neonates and infants with severe fungal infections not treatable with conventional agents. Fasano, C., O'Keeffe, J., Gibbs, D.[2019]

Fluconazole is an effective and well-tolerated treatment for systemic candidosis and candidemia in infants under 1 year old, based on a review of 78 studies involving 726 patients.

The recommended dosage for fluconazole is 6 mg/kg, with specific adjustments for neonates and those with renal impairment, highlighting the importance of age-related pharmacokinetics in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of fluconazole in children less than 1 year old: review]. Schwarze, R., Penk, A., Pittrow, L.[2019]

In a study of 173 children aged 4 months to 16 years, fluconazole demonstrated a high clinical efficacy, achieving a cure or improvement in 83% of children with confirmed fungal infections.

The safety profile of fluconazole was also favorable, with only 6% of patients experiencing related adverse events, indicating that it is a viable treatment option for pediatric patients with fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluconazole treatment of children with severe fungal infections not treatable with conventional agents. Fasano, C., O'Keeffe, J., Gibbs, D.[2019]

In a retrospective review of 30 children with candidemia, 18 episodes were successfully treated with a short course of 7 to 14 days of amphotericin B therapy after the last positive blood culture, indicating its efficacy in this population.

The study suggests that once the bloodstream is cleared of Candida and there are no signs of further infection, administering 0.5 mg/kg per day of amphotericin B for a short duration is sufficient for treating candidemia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course amphotericin B therapy for candidemia in pediatric patients. Donowitz, LG., Hendley, JO.[2013]

In a study analyzing 338 reports of anti-infective medication errors in pediatric patients, 13.6% of these errors reached the patients, with 1.5% resulting in harm that required additional medical intervention.

The majority of errors involved antibacterials, particularly beta-lactams, indicating that certain classes of anti-infective medications carry a higher risk of harmful errors, highlighting the need for improved safety measures in prescribing and administering these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology of and Risk Factors for Harmful Anti-Infective Medication Errors in a Pediatric Hospital. Modi, A., Germain, E., Soma, V., et al.[2022]

Fluconazole (FLCZ) demonstrated excellent clinical efficacy in treating gastrointestinal candidiasis in 2 out of 6 pediatric patients, while its effectiveness was poor in 3 cases of candidemia, likely due to severe underlying conditions and delayed treatment.

No side effects or laboratory abnormalities related to FLCZ were reported, indicating its safety; however, the study highlights the importance of early diagnosis and treatment for better outcomes in deep-seated mycosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluations of fluconazole in pediatric patients]. Sugita, K., Miyake, M., Takitani, K., et al.[2016]

Adverse drug reactions (ADRs) in children can significantly impact their health, with incidence rates estimated between 0.6% and 19.9%, and up to 6% of pediatric hospital admissions being linked to ADRs.

Efforts by pharmacovigilance centers aim to enhance the reporting and documentation of ADRs in children, which is crucial for understanding the relationship between drug use and clinical reactions, ultimately leading to safer and more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse drug reactions in children]. Jaffan, L., Läer, S.[2013]

Fluconazole is well tolerated and effective for treating systemic candidosis and candidaemia in infants under 1 year old, based on a review of 78 studies involving 726 children.

The recommended dosage for fluconazole in infants is 6 mg/kg/day, with specific adjustments for neonates and those with renal impairment, highlighting the importance of monitoring drug levels to maintain therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of fluconazole in children below 1 year of age. Schwarze, R., Penk, A., Pittrow, L.[2019]

In a study of 319 episodes of candidemia in children, 14.1% were classified as breakthrough candidemia, primarily caused by non-albicans Candida species, indicating a need for awareness of these less common strains.

Breakthrough candidemia was associated with more severe illness and higher mortality rates, suggesting that more aggressive treatment strategies are necessary to improve outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough candidemia in children: clinical and microbiological characteristics, therapeutic strategies and impact on outcomes. Lai, MY., Hsu, JF., Chu, SM., et al.[2020]

In a study of 335 pediatric patients receiving prolonged outpatient antimicrobials, 31.9% experienced adverse events (AEs), with diarrhea being the most common, affecting 29.1% of all AEs.

Serious AEs occurred in 12.5% of subjects, highlighting the importance of close monitoring for potential complications, such as allergic reactions and neutropenia, during extended antimicrobial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events in Pediatric Patients Receiving Long-Term Outpatient Antimicrobials. Olson, SC., Smith, S., Weissman, SJ., et al.[2022]

In a year-long study of 5,118 hospitalized children, 17.7% experienced at least one adverse drug reaction (ADR), highlighting the prevalence of ADRs in pediatric care.

Children who underwent general anesthesia (GA) were over six times more likely to develop an ADR, with opiate analgesics and GA drugs being major contributors, indicating a need for increased awareness and monitoring in pediatric surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children - a prospective observational cohort study of 6,601 admissions. Thiesen, S., Conroy, EJ., Bellis, JR., et al.[2022]

In a study of 772 hospitalized children under 6 years old in Barranquilla, Colombia, 19% experienced Adverse Drug Reactions (ADRs), highlighting a significant safety concern in pediatric medication use.

ADRs were more frequent in children under 2 years and in males, particularly among those receiving systemic antibiotics, indicating a need for careful monitoring in these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in hospitalized Colombian children. de Las Salas, R., Díaz-Agudelo, D., Burgos-Flórez, FJ., et al.[2022]

Candidemia, a serious fungal infection, is common in seriously ill or immunocompromised children, particularly caused by Candida albicans and Candida parapsilosis, leading to high morbidity and mortality; early antifungal therapy is crucial for better outcomes.

Current guidelines recommend using fluconazole or echinocandins for empiric therapy in high-risk pediatric patients, with echinocandins preferred for those with moderate-to-severe disease or recent azole exposure, highlighting the need for tailored treatment based on individual risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidemia in children. Zaoutis, T.[2022]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10912719

Short Course Versus Standard Course Antifungal Therapy for ... The primary objective of the proposed randomized trial is to determine if 7 days of therapy is comparable to 14 days for for pediatric uncomplicated candidemia ...

2. reporter.nih.gov reporter.nih.gov/project-details/11160661

A Multi-Center Randomized Controlled Trial The primary objective of the proposed randomized trial is to determine if 7 days of therapy is comparable to 14 days for for pediatric uncomplicated candidemia ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05763251?tab=table

Comparison of Uncomplicated Candidemia Therapy ... Researchers will compare no additional antifungal therapy (short-course) versus 7 additional days of systemic antifungal therapy (standard-course) in pediatric ...

4. academic.oup.com academic.oup.com/ofid/article/10/1/ofac656/6882745

Short Course of Antifungal Therapy in Patients With ... The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for ...

5. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(25)00409-8/fulltext

Towards shorter therapy for candidaemia: defining ... In this Review, outcome data were analysed to identify criteria differentiating between complicated and uncomplicated candidaemia in adults. We ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3651820/

Safety of fluconazole in paediatrics: a systematic review - PMC Fluconazole is relatively safe for paediatric patients. Hepatotoxicity and gastrointestinal toxicity are the most common adverse events.

7. withpower.com withpower.com/trial/phase-candidiasis-2-2023-847b4

Antifungal Therapy Duration for Candidemia in Children The treatment was well-tolerated, with only 5% of patients experiencing adverse events, indicating that fluconazole is a safe and effective option for young ...

8. idsociety.org idsociety.org/practice-guideline/candidiasis/

Candidiasis Chronic suppressive antifungal therapy with fluconazole, 400–800 mg (6–12 mg/kg) daily, is recommended to prevent recurrence (strong ...