Randomized Trial of Liposomal Amphotericin B for Histoplasmosis in AIDS Patients

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alessandro Pasqualotto
• Collaborators: Hospital de Clinicas de Porto Alegre; Hospital Nossa Senhora da Conceicao; Irmandade Santa Casa de Misericórdia de Porto Alegre
• Treatments: Amphotericin B; Liposomal amphotericin B

Criteria

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.