Phase III trial evaluating the safety and efficacy of a single high dose (10 mg/kg) of liposomal amphotericin B for disseminated histoplasmosis in AIDS patients, in comparison to standard therapy (3 mg/kg of liposomal amphotericin B for two weeks) (INDUCTION trial).
Adult patients admitted to the centers that will be part of the study
Infected by the HIV, regardless of the use of antiretroviral therapy
Patients diagnosed with disseminated histoplasmosis, confirmed by classical mycological methods (microscopy, culture or histopathology) or urinary Histoplasma antigen detection
Patients with central nervous system (CNS) infection may be included if they have an alternative diagnosis suggestive of another CNS infection
Refusal to participate in the trial
Previous diagnosis of histoplasmosis
Pregnant or lactating women
Patients with renal failure at any given time (serum creatinine > 2x or upper limit of normality (KDIGO, 2012)
Parallel
Single high dose of liposomal amphotericin B
DrugSingle high dose (10 mg/kg) of liposomal amphotericin B as induction therapy for disseminated histoplasmosis in AIDS
L-AmB standard dose
DrugStandard treatment (3 mg/kg for two weeks) with liposomal amphotericin B as induction therapy for disseminated histoplasmosis in AIDS
Overall survival rate
Overall mortality (from any cause) will be determined on day 14 of the study
Desirability of Outcome Ranking (DOOR) score
DOOR categorized as follows: (i) Death within the first 10 weeks of randomization or lost to follow up within 2 weeks (ii) SAE in the first 10 weeks (iii) Grade 4 laboratory abnormality in the first 2 weeks (electrolytes, anemia/leukopenia or renal dysfunction) (iv) Grade 3 laboratory abnormality in the first 2 weeks (electrolytes, anemia/leukopenia or renal dysfunction) or lost to follow up from 2-10 weeks (v) alive at week 10
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Safety outcomes will be evaluated using a clinical record, with continuous monitoring of the appearance of any suspected adverse event, since the first administration of the drug. The Frequency of grade 3 or 4 toxicities will be determined according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.
Clinical response rate
A successful clinical response to induction therapy will be defined as absence of fever for at least 72 hours and no increase in the severity of clinical signs, symptoms, or laboratory abnormalities attributable to histoplasmosis.
Rate of reduction in the concentration of Histoplasma urinary antigen
The effect of at least a 50% decrease in Histoplasma urinary antigen concentrations over the first two weeks of therapy will be determined.
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Federal University of Health Science of Porto Alegre
Lead sponsor
Gilead Sciences
Collaborator
Financiadora de Estudos e Projetos
Collaborator
Sociedade Gaucha de Infectologia
Collaborator
Immuno-mycologics, Inc. (IMMY)
Collaborator
