Randomized Trial of Liposomal Amphotericin B for Histoplasmosis in AIDS Patients

NCT04059770 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Three L-AmB Regimens in Histo
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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.

Conditions

Histoplasmosis; AIDS

Keywords

Histoplasmosis; AIDS; Liposomal amphotericin B; High dose therapy

Outcome Measures

Primary Outcomes (1)

• Clinical Response

  Maximum daily temperature lower than 37.8 °C

  day 14

Secondary Outcomes (1)

• Overall Mortality

  day 14

Study Arms (3)

single dose of L-AmB

EXPERIMENTAL

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

Drug: single dose of L-AmB

2 doses of L-AmB

EXPERIMENTAL

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

Drug: 2 doses of L-AmB

2 weeks of L-AmB

ACTIVE COMPARATOR

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

Drug: 2 weeks of L-AmB

Interventions

single dose of L-AmB DRUG

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

Also known as: Intervention 1

single dose of L-AmB

2 doses of L-AmB 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;

Also known as: Intervention 2

2 doses of L-AmB

2 weeks of L-AmB DRUG

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

Also known as: Intervention 3

2 weeks of L-AmB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alessandro Pasqualotto: lead
• Hospital de Clinicas de Porto Alegre: collaborator
• Hospital Nossa Senhora da Conceicao: collaborator
• Irmandade Santa Casa de Misericórdia de Porto Alegre: collaborator

Study Sites (1)

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

MeSH Terms

Conditions

Histoplasmosis; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Professor Alessandro C. Pasqualotto
• Organization: Universidade Federal de Ciências da Saúde de Porto Alegre

pasqualotto@ufcspa.edu.br

5551999951614

Study Officials

• Daiane Dalla Lana, PhD

  Federal University of Health Science of Porto Alegre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2019
• First Posted: August 16, 2019
• Study Start: February 14, 2020
• Primary Completion: December 31, 2021
• Study Completion: March 30, 2022
• Last Updated: March 14, 2025
• Results First Posted: March 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)