NCT06926569

Brief Summary

This study aims to compare the efficacy and safety of a single high-dose Liposomal Amphotericin B (L-AMB) against conventional Amphotericin B deoxycholate (AmBD) for HIV-associated Talaromycosis. The investigators hypothesize that L-AMB induction therapy (10 mg/kg) is non-inferior to AmBD (0.5-0.7 mg/kg/d) in efficacy and has an improved safety profile. The study's primary objective is to provide evidence supporting the guideline recommendation of single high-dose L-AMB for HIV-infected individuals with talaromycosis, while validating L-AMB's efficacy and safety in China. Study Design: Multi-center, randomized controlled trial comparing single high-dose L-AMB to guideline-recommended AmBD induction therapy for HIV-associated talaromycosis. Participants are HIV-infected adults (≥18 years) with confirmed talaromycosis by microscopy or culture. Interventions:

  • Primary: Proportion achieving clinical resolution on day 14.
  • Secondary: Overall survival, renal function, anemia, liver function, adverse events grade 3 or higher on day 14; time to clinical resolution and sterile blood cultures; survival, HIV viral suppression, CD4+ T-cell counts, adverse events (including IRIS), ART persistency, and patient-reported outcomes at weeks 4, 12, and 24. Sample Size: 58 participants per group (116 total), considering a 10% dropout rate.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
116

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started May 2025

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 21, 2025

Completed
23 days until next milestone

First Posted

Study publicly available on registry

April 13, 2025

Completed
18 days until next milestone

Study Start

First participant enrolled

May 1, 2025

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 5, 2026

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2026

Completed
Last Updated

April 13, 2025

Status Verified

April 1, 2025

Enrollment Period

8 months

First QC Date

March 21, 2025

Last Update Submit

April 7, 2025

Conditions

HIV/AIDS-associated Talaromycosis

Keywords

HIV/AIDS-associated talaromycosis

Outcome Measures

Primary Outcomes (1)

  • the proportion of participants who achieve clinical resolution on day 14

    The primary endpoint is the proportion of participants who achieve clinical resolution on day 14 . Clinical resolution defined as resolution of symptoms/signs attributable to talaromycosis, such as fever and rash (temperature below 38 for more than 3 days, improvement of rash) and sterile blood cultures, except for manifestations that are expected to last for more than 14 days after treatment initiation: hepatosplenomegaly, jaundice and pancytopenia.

    14 days

Secondary Outcomes (8)

  • Overall Survival

    14 days

  • Adverse Events

    14 days

  • The Time to Clinical Resolution

    one year

  • The Time to Achieve Sterile Blood Cultures

    14 days

  • HIV viral suppression

    24 weeks

  • +3 more secondary outcomes

Study Arms (2)

Single high-dose L-AmB group

EXPERIMENTAL

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy.

Drug: AmBisome

Control group

OTHER

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy.

Drug: Amphotericin B

Interventions

Amphotericin BDRUG

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy

Control group
AmBisomeDRUG

After enrollment, participants will be 1:1 randomly assigned into two groups for induction therapy after informed consent: single high-dose L-AmB group (10 mg/kg single intravenous dose of L-AMB) and control group (amphotericin B deoxycholate(AmBD) at 0.5-0.7 mg/kg/d intravenously for 14 days as the standard of care recommended by local guidelines).Thereafter, all participants in both groups will start consolidation therapy within 24 hours of the induction treatment, 200mg itraconazole(or voriconazole) q12h will be given for 10 weeks. After consolidation therapy, all participants will take oral itraconazole 200mg qd as secondary prophylaxis until their CD4+ cell counts are higher than 100cells/mm3 for at least 6 months. For the antiretroviral therapy, all participants will start B/F/TAF qd within 7 days after initiating antifungal therapy.

Single high-dose L-AmB group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 18 and above
  • ART naive
  • HIV positive individuals
  • Confirmed Talaromycosis diagnosed by culture/microscopy

You may not qualify if:

  • Pregnancy or lactating women;
  • Central nervous system involvement (assessed either through clinical manifestations or cerebrospinal fluid analysis);
  • Known allergy to AMB d/L-AMB, or the concomitant use of medications known to interact with AMB d/L-AMB;
  • Alanine aminotransferase or aspartate aminotransferase levels exceeding 400 U/L;
  • Absolute neutrophil count below 500/mm3;
  • Creatinine clearance below 30 mL/min (calculated using the Cockcroft and Gault equation);
  • Concurrent diagnosis of cryptococcal meningitis;
  • Concurrent treatment with rifampicin;
  • Previous treatment for talaromycosis lasting more than 48 hours.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (12)

  • Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, Cuong DD, Phuc PTH, Vinh VH, Hanh DTH, Tam VV, Thanh NT, Thuy TP, Hang NT, Long HB, Nhan HT, Wertheim HFL, Merson L, Shikuma C, Day JN, Chau NVV, Farrar J, Thwaites G, Wolbers M; IVAP Investigators. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med. 2017 Jun 15;376(24):2329-2340. doi: 10.1056/NEJMoa1613306.

    PMID: 28614691BACKGROUND

  • Adler-Moore J, Lewis RE, Bruggemann RJM, Rijnders BJA, Groll AH, Walsh TJ. Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B. Clin Infect Dis. 2019 May 2;68(Suppl 4):S244-S259. doi: 10.1093/cid/ciz064.

    PMID: 31222254BACKGROUND

  • Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010 Feb 11;362(6):504-12. doi: 10.1056/NEJMoa0903627.

    PMID: 20147716BACKGROUND

  • Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, Rutakingirwa MK, Ssebambulidde K, Tugume L, Rhein J, Boulware DR, Mwandumba HC, Moyo M, Mzinganjira H, Kanyama C, Hosseinipour MC, Chawinga C, Meintjes G, Schutz C, Comins K, Singh A, Muzoora C, Jjunju S, Nuwagira E, Mosepele M, Leeme T, Siamisang K, Ndhlovu CE, Hlupeni A, Mutata C, van Widenfelt E, Chen T, Wang D, Hope W, Boyer-Chammard T, Loyse A, Molloy SF, Youssouf N, Lortholary O, Lalloo DG, Jaffar S, Harrison TS; Ambition Study Group. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med. 2022 Mar 24;386(12):1109-1120. doi: 10.1056/NEJMoa2111904.

    PMID: 35320642BACKGROUND

  • Chinese guidelines for diagnosis and treatment of human immunodeficiency virus infection/acquired immunodeficiency syndrome (2024 edition), 10.3760/cma.j.cn311365-20240328-00081.

    BACKGROUND

  • 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: 37232940BACKGROUND

  • Bicanic T, Bottomley C, Loyse A, Brouwer AE, Muzoora C, Taseera K, Jackson A, Phulusa J, Hosseinipour MC, van der Horst C, Limmathurotsakul D, White NJ, Wilson D, Wood R, Meintjes G, Harrison TS, Jarvis JN. Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis. Antimicrob Agents Chemother. 2015 Dec;59(12):7224-31. doi: 10.1128/AAC.01698-15. Epub 2015 Sep 8.

    PMID: 26349818BACKGROUND

  • Ullmann AJ. Nephrotoxicity in the setting of invasive fungal diseases. Mycoses. 2008;51 Suppl 1:25-30. doi: 10.1111/j.1439-0507.2008.01525.x.

    PMID: 18471158BACKGROUND

  • Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-andadolescent-opportunistic-infection. Accessed 25/6/2024

    BACKGROUND

  • Wang F, Han R, Chen S. An Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei. Clin Microbiol Rev. 2023 Mar 23;36(1):e0005122. doi: 10.1128/cmr.00051-22. Epub 2023 Jan 17.

    PMID: 36648228BACKGROUND

  • Guo P, Li L, Tang X. Advances in diagnosis and treatment of talaromycosis in patients with AIDS. Chin Med J (Engl). 2022 Nov 20;135(22):2687-2689. doi: 10.1097/CM9.0000000000002506. No abstract available.

    PMID: 36719357BACKGROUND

  • Yan X, Meng X, Song W, Liu L, Chen J, Zhang R, Shen Y. Single high-dose liposomal amphotericin B plus B/F/TAF for AIDS-associated talaromycosis in China: a multicentre randomised controlled trial protocol. BMJ Open. 2025 Nov 19;15(11):e105648. doi: 10.1136/bmjopen-2025-105648.

    PMID: 41263912DERIVED

MeSH Terms

Interventions

Amphotericin Bliposomal amphotericin B

Intervention Hierarchy (Ancestors)

MacrolidesPolyketidesLactonesOrganic Chemicals

Central Study Contacts

Shen Yinzhong Dr.

CONTACT

+8618916113951shenyinzhong@shphc.org.cn

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 21, 2025

First Posted

April 13, 2025

Study Start

May 1, 2025

Primary Completion

January 5, 2026

Study Completion

May 1, 2026

Last Updated

April 13, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share