Antifungal Therapy Duration for Candidemia in Children

(COUNT Trial)

Recruiting at 16 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

Trial Summary

What is the purpose of this 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.

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.

What data supports the effectiveness of the drug fluconazole (Diflucan) for treating candidemia in children?

Research shows that fluconazole is effective in treating severe fungal infections in children, with a clinical cure or improvement in 83% of cases. However, its effectiveness in candidemia specifically may be limited if treatment is delayed, highlighting the importance of early diagnosis and treatment. ^{1 2 3 4 5}

Is antifungal therapy, like fluconazole (Diflucan), generally safe for children?

There is limited data on the safety of antifungal treatments like fluconazole in children, but adverse drug reactions (unwanted side effects) are a known issue in pediatric medicine, with rates of such reactions varying widely. It's important to monitor for any side effects when children are on long-term antimicrobial treatments. ^{6 7 8 9 10}

How does the drug fluconazole differ from other treatments for candidemia in children?

Fluconazole is unique because it can be administered both orally and intravenously, has a long plasma half-life, and is effective in children where conventional antifungal therapies are ineffective or not suitable. It is particularly beneficial for severe fungal infections in children, including those with underlying conditions like cancer or after transplantation, and is well-tolerated even in very young infants. ^{3 4 11 12 13}

Research Team

William J Steinbach, MD

Principal Investigator

Arkansas Children's Hospital Research Institute

Brian Fisher, DO

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

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

I am older than 120 days but younger than 18 years and had a positive blood culture.

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

Exclusion Criteria

Previous enrollment in this trial

I need antifungal medication due to an underlying condition.

I am currently on antifungal treatment for a serious fungal infection.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Candidemia in children. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Short-course amphotericin B therapy for candidemia in pediatric patients. [2013]

3. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluations of fluconazole in pediatric patients]. [2016]

4. Germany pubmed.ncbi.nlm.nih.gov

Fluconazole treatment of children with severe fungal infections not treatable with conventional agents. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Breakthrough candidemia in children: clinical and microbiological characteristics, therapeutic strategies and impact on outcomes. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Adverse Events in Pediatric Patients Receiving Long-Term Outpatient Antimicrobials. [2022]

7. Colombia pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in hospitalized Colombian children. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Adverse drug reactions in children]. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Epidemiology of and Risk Factors for Harmful Anti-Infective Medication Errors in a Pediatric Hospital. [2022]

10. England 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. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Administration of fluconazole in children below 1 year of age. [2019]

12. Germany pubmed.ncbi.nlm.nih.gov

Fluconazole treatment of neonates and infants with severe fungal infections not treatable with conventional agents. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

[Use of fluconazole in children less than 1 year old: review]. [2019]