Randomized Trial of Liposomal Amphotericin B for Histoplasmosis in AIDS Patients

NCT ID: NCT04059770

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-14
• Study Completion Date: 2022-03-30

Brief 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.

Detailed Description

This is a prospective randomized non-comparative multicenter open label trial of induction therapy with LAmB for DH in AIDS patients, followed by oral therapy with itraconazole.

The sample size planned is 99 patients of both sexes, older than 18 years (33 patients per study arm), infected with HIV and with confirmed diagnosis for DH. This sample size considers 10% of dropout.

The study will be conducted in accordance with the Helsinki Declaration, as well as the Standards national and international Guidelines for Good Clinical Practices.

Eight research centres in Brazil will competitively recruit patients: Santa Casa de Misericórdia de Porto Alegre (Porto Alegre; Dr Alessandro C. Pasqualotto), Hospital de Clínicas de Porto Alegre (Porto Alegre; Dr Diego R. Falci), Hospital Nossa Senhora da Conceição (Porto Alegre; Dr Marineide Melo), Hospital de Doenças Tropicais (Goiânia; Dr Cassia S. de Miranda Godoy), Hospital São José de Doenças Infecciosas (Fortaleza; Dr Terezinha M. J. Silva Leitão), and Hospital Giselda Trigueiro (Natal, Dr Monica B. Bay), Hospital Universitário Osvaldo Cruz (Recife, Dr. Filipe Prohaska Batista) e Instituto de Infectologia Emília Ribas (São Paulo, Dr. José Ernesto Vidal Bermudez).

AIDS patients with DH will be randomized to one of three study arms:

(i) single IV dose of 10 mg/kg of L-AmB; (ii) single IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; (iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.

Induction therapy will be followed in all patients by oral therapy with itraconazole capsules at 400 mg/daily for a year, azole drug which is already therapy of choice for consolidation of histoplasmosis, according to national and international Guidelines.

Conditions

Histoplasmosis; AIDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

single dose of L-AmB

single IV dose of 10 mg/kg of L-AmB on day 1;

Group Type: EXPERIMENTAL

single dose of L-AmB

Intervention Type: DRUG

(i) single IV dose of 10 mg/kg of L-AmB on day 1;

2 doses of L-AmB

IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3;

Group Type: EXPERIMENTAL

2 doses of L-AmB

Intervention Type: DRUG

(ii) IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3;

2 weeks of L-AmB

IV dose of 3 mg/kg of L-AmB for 2 weeks.

Group Type: ACTIVE_COMPARATOR

2 weeks of L-AmB

Intervention Type: DRUG

(iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.

Interventions

single dose of L-AmB

(i) single IV dose of 10 mg/kg of L-AmB on day 1;

Intervention Type: DRUG

2 doses of L-AmB

(ii) IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3;

Intervention Type: DRUG

2 weeks of L-AmB

(iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.

Intervention Type: DRUG

Other Intervention Names

Intervention 1; Intervention 2; Intervention 3

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: collaborator

Hospital Nossa Senhora da Conceicao

OTHER

Sponsor Role: collaborator

Irmandade Santa Casa de Misericórdia de Porto Alegre

OTHER

Sponsor Role: collaborator

Alessandro Pasqualotto

OTHER

Sponsor Role: lead

Responsible Party

Alessandro Pasqualotto

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daiane Dalla Lana, PhD

Role: STUDY_CHAIR

Federal University of Health Science of Porto Alegre

Locations

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Three L-AmB Regimens in Histo

Identifier Type: -

Identifier Source: org_study_id