HistoplasmosisPhase 2NCT04059770

Randomized Trial of Liposomal Amphotericin B for Histoplasmosis in AIDS Patients

A Phase 2 study testing single dose of L-AmB, 2 doses of L-AmB and 2 weeks of L-AmB in people with Histoplasmosis and AIDS, run by Alessandro Pasqualotto at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Histoplasmosis, AIDS
What is being tested?: single dose of L-AmB, 2 doses of L-AmB and 2 weeks of L-AmB
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 118 participants
Where: 1 siteBrazil
Study dates: 14 Feb 2020to 30 Mar 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 11Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Irmandade da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90020-090

Other trials in Brazil

About this study

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

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.

Read the 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
Being tested: single dose of L-AmB, 2 doses of L-AmB, 2 weeks of L-AmB
Keywords: Histoplasmosis, AIDS, Liposomal amphotericin B, High dose therapy
Medical subject headings: Histoplasmosis, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

single dose of L-AmBDrug
Also called Intervention 1
(i) single IV dose of 10 mg/kg of L-AmB on day 1;
2 doses of L-AmBDrug
Also called Intervention 2
(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-AmBDrug
Also called Intervention 3
(iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.

Study groups in NCT04059770
Study group	Role	What they receive
single dose of L-AmB	Experimental	single IV dose of 10 mg/kg of L-AmB on day 1; Receives: 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; Receives: 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. Receives: Drug: 2 weeks of L-AmB

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical Response
Maximum daily temperature lower than 37.8 °C
Measured: day 14

Secondary outcomes (1)

Overall Mortality
Mortality rates attributed to the cause of death that is not directly and only related to histoplasmosis
Measured: day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Feb 202030 Mar 2022

First posted16 Aug 2019
Study start14 Feb 2020
Primary completion31 Dec 2021
Study completion30 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HistoplasmosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 118 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04059770
Sponsor's protocol ID: Three L-AmB Regimens in Histo
Status last verified: Feb 2025
First submitted: 1 Apr 2019
Last updated: 14 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Platform Trial for Salvage Consolidation Therapy in Dimorphic Fungi
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RecruitingPhase 3
Efficacy and Safety of High-dose Liposomal Amphotericin B for Disseminated Histoplasmosis in AIDS
Disseminated Histoplasma Capsulatum Infection, AIDS and Infections
RecruitingPhase 4
A Prospective Longitudinal Analysis of Faricimab (Vabysmo 6mg) For Choroidal Neovascularization in Presumed Ocular Histoplasmosis Syndrome
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All Histoplasmosis trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open Label Phase-II Randomized Trial of Three Liposomal Amphotericin B Regimens as Induction Therapy for Disseminated Histoplasmosis in AIDS Patients
ClinicalTrials.gov ID: NCT04059770
Acronym / sponsor ID: Three L-AmB Regimens in Histo
Conditions: Histoplasmosis, AIDS
Keywords: Histoplasmosis, AIDS, Liposomal amphotericin B, High dose therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 118 participants (actual)
Lead sponsor: Alessandro PasqualottoUniversity, hospital or other
Collaborators: Hospital de Clinicas de Porto Alegre, Hospital Nossa Senhora da Conceicao, Irmandade Santa Casa de Misericórdia de Porto Alegre
Study start: 14 Feb 2020 (actual)
Primary completion: 31 Dec 2021 (actual)
Study completion: 30 Mar 2022 (actual)
First posted: 16 Aug 2019 (actual)
Results: Posted 14 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
single dose of L-AmB	Experimental	Drug: single dose of L-AmBsingle IV dose of 10 mg/kg of L-AmB on day 1;
2 doses of L-AmB	Experimental	Drug: 2 doses of L-AmBIV 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	Active comparator	Drug: 2 weeks of L-AmBIV dose of 3 mg/kg of L-AmB for 2 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
single dose of L-AmBAlso: Intervention 1(i) single IV dose of 10 mg/kg of L-AmB on day 1;	Drug	single dose of L-AmB
2 doses of L-AmBAlso: Intervention 2(ii) 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-AmBAlso: Intervention 3(iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.	Drug	2 weeks of L-AmB

Primary outcome

Clinical Response
Time frame: day 14
Maximum daily temperature lower than 37.8 °C

1 secondary outcome

Overall Mortality
Time frame: day 14

Results and safety

Results posted to the registry on 14 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Single Dose of L-AmB	40	40
2 Doses of L-AmB	39	39
2 Weeks of L-AmB	39	39

Primary outcome: Clinical Response

Time frame: day 14. Count of participants. Unit: Participants

Measure	Single Dose of L-AmB n = 38	2 Doses of L-AmB n = 36	2 Weeks of L-AmB n = 38
Value	32	25	28

Population analysed: Clinical response on day 14 was 84.0% for the single-dose L-AmB arm-(32/38-1 patient was excluded due to concomitant tuberculosis, and another was lost to follow-up), 69.0% (25/36) for the 2-dose L-AmB arm, with 3 patients being excluded from efficacy analysis (1 individual with central nervous system histoplasmosis, 1 patient with concomitant tuberculosis, and another patient lost to follow-up); in the control group, response rate was 74.0% (28/38), with 1 patient being lost to follow-up.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 14 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Single Dose of L-AmB	1 of 38 (2.6%)	34 of 38 (89.5%)	4 of 38
2 Doses of L-AmB	6 of 37 (16.2%)	27 of 37 (73%)	8 of 37
2 Weeks of L-AmB	4 of 38 (10.5%)	34 of 38 (89.5%)	3 of 38

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Histoplasmosis

Not yet recruitingPhase 3
Histoplasmosis Induction and Consolidation Therapy Factorial Randomized Clinical Trial (Histo-FACT)
Histoplasmosis
Not yet recruitingObservational study
Assessment of the Risk of Zoonotic Infections in Prisons in French Guiana
Q Fever, Leptospirosis
Not yet recruitingPhase 2
Platform Trial for Salvage Consolidation Therapy in Dimorphic Fungi
Coccidioidomycosis, Blastomycosis
RecruitingPhase 3
Efficacy and Safety of High-dose Liposomal Amphotericin B for Disseminated Histoplasmosis in AIDS
Disseminated Histoplasma Capsulatum Infection, AIDS and Infections
RecruitingPhase 4
A Prospective Longitudinal Analysis of Faricimab (Vabysmo 6mg) For Choroidal Neovascularization in Presumed Ocular Histoplasmosis Syndrome
Presumed Ocular Histoplasmosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daiane Dalla Lana, PhD study chair

Federal University of Health Science of Porto Alegre

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing single dose of L-AmB, 2 doses of L-AmB and 2 weeks of L-AmB in people with Histoplasmosis and AIDS, run by Alessandro Pasqualotto at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Response (time frame: day 14). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04059770.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.