Open Label Phase-II Randomized Trial of Three Liposomal Amphotericin B Regimens as Induction Therapy for Disseminated Histoplasmosis in AIDS Patients

Three L-AmB Regimens in Histo

Disseminated histoplasmosis (DH) is one of the major AIDS-defining infections responsible for high mortality rates in HIV-infected patients. Liposomal amphotericin B (L-AmB) is considered the therapy of choice for AIDS-associated histoplasmosis.However, many patients in Latin America are still treated with high doses of deoxycholate amphotericin B (d-AmB) for long periods. These regimens are associated with toxicity and thus reduced efficacy. Therefore, a better treatment strategy is necessary to improve the activity of this amphotericin B treatment. Treatment with a high dose of L-AmB for short periods (rather than standard doses for longer periods) is a promising approach considering that the antifungal effect of amphotericin B depends on peak concentrations. This randomized open-label Phase II study aims to determinate and to compare the activity and safety of three L-AmB regimens, as induction therapy for DH in AIDS patients.

2020-02-14

2021-12-31

2022-03-30

Completed

Early phase I

99

Inclusion Criteria: * Adult (\> 18 years) HIV-infected hospitalized patients diagnosed with HD by the means of (i) urine Histoplasma positive antigen (IMMY® monoclonal antibody test); (ii) confirmation by classical mycological methods (microscopy, culture or histopathology); or (iii) Histoplasma positive qualitative polymerase chain reaction (PCR) in bronchoalveolar lavage samples, bone marrow aspirates or tissue samples. * Patients will be included despite of the use of antiretroviral therapy (ART). * Understanding and signed the Informed Consent Form. Exclusion Criteria: * Patients with previous diagnosis of histoplasmosis. * Pregnant or lactating women. * Patients with renal insufficiency (serum creatinine and urea \> 1.5x the upper limit of normal). * Abnormal aminotransferases (up to \> 3x the upper limit of normal) and patients with a severe prior reaction to polyene antifungal. * Patients who have received more than one dose of a polyene antifungal in the last 48 hours. * Patients who refuse to participate in the study. * Patients diagnosed with histoplasmosis that affect the central nervous system. * Patients who, at the trial of the attending physician, are expected to die within 48 hours. * Patients diagnosed with tuberculosis. * Patients with any disease or condition that, in the opinion of the investigator, may interfere with the assessments or participation in the study. * Patients receiving drugs that cause significant (relative or absolute) drug interaction with Itraconazole.

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2023-03-21