Efficacy and Safety of High-dose Liposomal Amphotericin B for Disseminated Histoplasmosis in AIDS

NCT05814432 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 67938323.0.1001.5345
• Study Type: interventional
• Target: 279
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Disseminated Histoplasma Capsulatum Infection; AIDS and Infections; Immunosuppression; Fungal Infection

Keywords

Disseminated Histoplasmosis; AIDS; Liposomal amphotericin B; Fungal infection

Outcome Measures

Primary Outcomes (1)

• Overall survival rate

  Overall mortality (from any cause) will be determined on day 14 of the study

  14 days

Secondary Outcomes (7)

• Desirability of Outcome Ranking (DOOR) score

  Evaluated on week 10

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Evaluated on day 14

• Clinical response rate

  Evaluated on day 14

• Rate of reduction in the concentration of Histoplasma urinary antigen

  Evaluated on day 14

• Fungal load reduction rate in blood samples

  Evaluated on day 14

Study Arms (2)

Single high dose arm

EXPERIMENTAL

Single high dose of liposomal amphotericin B (10 mg/kg)

Drug: Single high dose of liposomal amphotericin B

Standard dose arm

ACTIVE COMPARATOR

Standard treatment with 3 mg/kg of liposomal amphotericin B daily for 2 weeks

Drug: L-AmB standard dose

Interventions

Single high dose of liposomal amphotericin B DRUG

Single high dose (10 mg/kg) of liposomal amphotericin B as induction therapy for disseminated histoplasmosis in AIDS

Also known as: L-AmB single high dose investigational arm

Single high dose arm

L-AmB standard dose DRUG

Standard treatment (3 mg/kg for two weeks) with liposomal amphotericin B as induction therapy for disseminated histoplasmosis in AIDS

Also known as: L-AmB conventional therapy

Standard dose arm

Eligibility Criteria

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

You may qualify if:

• 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
• Patients using fluconazole for oroesophageal candidiasis may be included

You may not qualify if:

• 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)
• Previous severe reaction to a polyene antifungal
• Receipt of more than one dose of a polyene antifungal in the last 48 h
• Suspected histoplasmosis involving the central nervous system
• Patients who, in the judgment of the attending physician, have the prospect of death within the next 48 hours after selection, will also be excluded
• Patients with suspected histoplasmosis involving the central nervous system (CNS), as this condition requires high doses of amphotericin B
• Patients with the prospect of death in the next 48 hours after selection
• Patients with a concomitant diagnosis of cryptococcus will be excluded, as will patients with leishmaniasis in treatment or in secondary prophylaxis with amphotericin
• Patients without the capacity to administer enteral medication-at the discretion of the principal investigator of each center-considering that these patients will not be able to use itraconazole orally or through a feeding tube

Sponsors & Collaborators

• Federal University of Health Science of Porto Alegre: lead
• Gilead Sciences: collaborator
• Financiadora de Estudos e Projetos: collaborator
• Sociedade Gaucha de Infectologia: collaborator
• Immuno-mycologics, Inc. (IMMY): collaborator

Study Sites (5)

Hospital de Doenças Tropicais

Goiânia, Goiás, Brazil

RECRUITING

Hospital Giselda Trigueiro

Natal, Rio Grande do Norte, Brazil

RECRUITING

Federal University of Health Sciences of Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

RECRUITING

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

RECRUITING

Hospital Geral de Roraima

Boa Vista, Roraima, Brazil

RECRUITING

Related Publications (1)

• Pasqualotto AC, Lana DD, Godoy CSM, Leitao TDMJS, Bay MB, Damasceno LS, Soares RBA, Kist R, Silva LR, Wiltgen D, Melo M, Guimaraes TF, Guimaraes MR, Vechi HT, de Mesquita JRL, Monteiro GRG, Adenis A, Bahr NC, Spec A, Boulware DR, Israelski D, Chiller T, Falci DR. Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial. Clin Infect Dis. 2023 Oct 13;77(8):1126-1132. doi: 10.1093/cid/ciad313.

  PMID: 37232940 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Infections; Mycoses; Histoplasmosis

Interventions

Single Person; liposomal amphotericin B

Condition Hierarchy (Ancestors)

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; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Officials

• Daiane F Dalla Lana, PhD

  Federal University of Health Science of Porto Alegre

  STUDY CHAIR

• Renata B Ascenco Soares, PhD

  HDT - SES/GO

  STUDY CHAIR

• Luana C Genz Bazana, PhD

  Federal University of Health Science of Porto Alegre

  STUDY CHAIR

• Tarsila Vieceli, MD MSc

  Federal University of Health Science of Porto Alegre

  STUDY CHAIR

Central Study Contacts

Alessandro C Pasqualotto, MD PhD

CONTACT

+5551999951614; acpasqualotto@hotmail.com

Diego R Falci, MD PhD

CONTACT

+5551997507835; diego.falci@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medicine Professor, Head of Infectology

Model Details: Clinical assessments will take place at the start of the study (patient enrollment), day 3, day 7, day 14 (survival status) and week 10. During the study visits, some data and tests will be collected such as: maximum temperature, presence of dyspnea, respiratory rate, need for mechanical ventilation, systolic blood pressure, World Health Organization performance status, Karnofsky scale, Glasgow coma scale, biochemical laboratory tests, documentation of HIV infection, CD4 and CD8 counts, pregnancy test, urine test for Histoplasma antigen, blood sample for Histoplasma PCR. A 10-week visit will be carried out to also determine survival status, including whether or not there was a need for additional courses of amphotericin B, whether or not the patient had immune reconstitution syndrome, whether they had any serious adverse events, and finally, the DOOR score.

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: April 14, 2023
• Study Start: January 16, 2025
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): November 28, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (5)