Evaluation of Short-Duration Antifungal Therapy with Voriconazole, Anidulafungin, and Caspofungin in Uncomplicated Candidemia: A Randomized Controlled Trial

The primary objective is to demonstrate the non-inferiority of a 7-day treatment duration after the first negative blood culture compared to a 14-day duration for all-cause mortality at Day 28 in patients with uncomplicated candidemia. The secondary objectives include:

• Evaluation of clinical efficacy and the absence of secondary localization of the infection.
• Assessment of the incidence of deaths attributable to the infection up to Day 28.
• Monitoring of hepatic tolerance through clinical and biological parameters until Day 14.
• Estimation of cost-effectiveness regarding the shortened treatment duration.
• Evaluation of relapse and secondary localization at Day 45.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, both male and female, diagnosed with uncomplicated candidemia. Inclusion requires a positive Candida sp. blood culture obtained less than 72 hours prior to enrollment and a predicted life expectancy exceeding four weeks. Patients presenting with aplasia, characterized by a neutrophil count below 500/mm³, must have a predicted duration of this condition of less than 7 days.

This Phase III randomized clinical trial is designed to evaluate the non-inferiority of a short-duration antifungal therapy compared to a standard duration in patients with uncomplicated candidemia. The primary objective is to demonstrate that a treatment duration of 7 days after the first negative blood culture is non-inferior to a 14-day duration regarding all-cause mortality at Day 28. The study involves the administration of various antifungal agents, including anidulafungin, caspofungin, fluconazole, micafungin, voriconazole, and amphotericin B, liposomal, as either test or comparator products. The research methodology includes several scheduled visits: an initial screening visit (Visit 1) to assess inclusion criteria, a randomization visit (Visit 2), a follow-up visit at Day 14 (Visit 3) to monitor liver function tests, and a subsequent visit (Visit 4) to assess cost-effectiveness. Additional secondary endpoints include the evaluation of relapse and secondary localizations at Day 45. The total duration of the study recruitment is expected to span from November 2025 to January 2028.

Anidulafungin is administered via intravenous route at a dosage of 200 mg as an experimental treatment.

Amphotericin B, liposome is administered via intravenous route at a dosage of 5 mg/kg as an experimental treatment.

Caspofungin is administered via intravenous route at a dosage of 70 mg as an experimental treatment.

Fluconazole is administered via oral route at a dosage of 12 mg/kg as an experimental treatment.

Micafungin is administered via intravenous route at a dosage of 100 mg as an experimental treatment.

Voriconazole is administered via oral route at a dosage of 12 mg/kg as an experimental treatment.

The following substances are utilized as comparator treatments:

• Anidulafungin administered via intravenous route at a dosage of 200 mg.
• Amphotericin B, liposome administered via intravenous route at a dosage of 5 mg/kg.
• Caspofungin administered via intravenous route at a dosage of 70 mg.
• Fluconazole administered via oral route at a dosage of 12 mg/kg.
• Micafungin administered via intravenous route at a dosage of 100 mg.
• Voriconazole administered via oral route at a dosage of 12 mg/kg.

The primary efficacy endpoint is all-cause mortality (ACM) assessed at Day 28 (+/- 2 days) following the first negative blood culture in randomized patients diagnosed with uncomplicated candidemia. Secondary efficacy parameters include:

• The proportion of randomized patients experiencing secondary localizations.
• The cumulative incidence of death related to fungal infection at Day 28 (+/- 2 days) after the first negative blood culture.
• The proportion of randomized patients experiencing relapse at Day 45 (+/- 2 days).
• The proportion of randomized patients with secondary localization at Day 45 (+/- 2 days).