Liposomal Amphotericin B and Flucytosine Antifungal Strategy for Talaromycosis (LAmB-FAST)
Duke University
Summary
LAmB-FAST is a factorial randomized controlled trial simultaneously testing two interventions in one trial. LAmB-FAST seeks to inform treatment guidelines on the induction and maintenance therapy of HIV-associated talaromycosis (formerly called penicilliosis) and will answer the following three questions: 1. Is induction therapy using a single 10 mg\\/kg dose of liposomal amphotericin B (LAmB) is more effective than 14 days of the conventional deoxycholate amphotericin B (DAmB)? 2. Is adding flucytosine (5FC) to amphotericin B more effective than amphotericin B alone? 3. Is HIV viral load guided stopping of itraconazole maintenance therapy as effective as the current CD4 guided strategy in the prevention of talaromycosis relapse?
Description
Talaromycosis (formerly known as penicilliosis) is caused by the dimorphic fungus Talaromyces marneffei (Tm) endemic in Southeast Asia where it is a leading the cause of death among people with advanced HIV disease (AHD, CD4 count \<200 cells/mm3 and/or WHO disease stage III or IV). Despite the mortality on treatment as high as 30%, current treatment options are limited to just two drugs: amphotericin B deoxycholate (DAmB) - which has substantial toxicity, and itraconazole - which has poor bioavailability. As a roadmap to identify safer and more effective antifungal strategies, LAmB-FAST appl…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * HIV infected adults (age greater or equal to 18), on ART or no ART * Definitive talaromycosis confirmed by microscopy, histology, or culture Exclusion Criteria: * Known severe allergy to AmB or 5FC * Absolute neutrophil count \<500 cells * Concurrent cryptococcal or TB meningitis * Received \> 2 doses of DAmB * Pregnancy
Interventions
- DrugLiposomal Amphotericin B (LAmB)
Antifungal dosed at 10 mg/kg/day IV x one single dose.
- DrugFlucytosine (5FC)
Antifungal dosed at 25mg/kg oral 3x daily.
- DrugFlucytosine (5FC) placebo pill
Similar in appearance to flucytosine. Also dosed at 25mg/kg oral 3x daily.
- DrugDeoxycholate Amphotericin B (DAmB)
Antifungal dosed at 0.7 mg/kg/day IV x 2 weeks.
Locations (5)
- Duke University Medical CenterDurham, North Carolina
- Bach Mai HospitalHanoi
- National Hospital for Tropical DiseasesHanoi
- Hospital for Tropical DiseasesHo Chi Minh City
- Pham Ngoc Thach University of MedicineHo Chi Minh City