Comparative Study of Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin Sequential Itraconazole Therapy (CSHHTVASIT)

Guangxi Medical University

Status: Unknown

Conditions: Talaromyces in Human Immunodeficiency Virus Negative; To Compare Voriconazole and Amphotericin Sequential Itraconazole Therapy; To Dynamically Monitor the Anti-Interferon-γ Autoantibodies

Treatments: Drug: Voriconazole

Study type: Interventional

Funder types: Other

Identifiers

NCT03827278

TSM-AMB-VOR-2018

Details and patient eligibility

About

Through a multi-center large-sample non-randomized controlled study, the effect of voriconazole, amphotericin B sequential itraconazole therapy on Talaromyces in Human Immunodeficiency Virus（HIV）negative hosts were compared to clarify whether the two therapies were equivalent; A comprehensive efficacy evaluation system and standard treatment program was established to provide a basis for standardized treatment of Talaromyces in Human Immunodeficiency Virus negative hosts.The observational indicators included: 2-week all-cause mortality; 24-week all-cause mortality; clinical improvement time; level of decrease of fungus in the blood culture medium two weeks before treatment; recurrence; appearance of adverse drug reaction at the level 3 and above. Dynamically monitor the immune cells and factors like anti-Interferon-γ autoantibodies, Interferon-γ, Th1/Th2, and Th17/Treg in the HIV-negative Talaromyces host microenvironment, and observe the host's immune status and its change. 3. study the effect of absence of Interferon-γ and Interferon-γ Receptor (IFN-γR）on the activation and function of anti-Interferon-γ autoantibodies, Th1/Th2, and Th17/Treg by establishing a Talaromyces mouse model that knocks out the Interferon-γ and IFN-γR gene and a IFN-γ silenced cell model; Study the effect of anti-IFN-γ autoantibody on the activation and function of IFN-γ、Th1/Th2、Th17/Treg by increasing its titer in vitro and vivo; determine by which path the anti-IFN-γ autoantibody of HIV-negative host influences its immune regulation mechanism; finally, the intervention effect of IFN-γ on high titer anti-IFN-γ autoantibodies is studied, providing a new idea for immunotargeted therapy.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. HIV-negative adults (≥18 years of age) who diagnosis of talaromyces that was confirmed by either microscopy or culture
2. Must be able to swallow tablets

Exclusion criteria

1. Pregnancy, central nervous system involvement assessed either clinically or by analyses of cerebrospinal fluid
2. An allergy to voriconazole, itraconazole or amphotericin
3. The concomitant use of certain medications that interact with voriconazole, itraconazole or amphotericin
4. An alanine aminotransferase or aspartate aminotransferase level of more than 400 U per liter
5. An absolute neutrophil count of less than 500 per cubic millimeter
6. A creatinine clearance of less than 30 ml per minute (calculated by the method of Cockcroft and Gault)
7. a concurrent diagnosis of cryptococcal meningitis
8. concurrent treatment with rifampicin
9. previous treatment for talaromyces for more than 48 hours
10. HIV positive who diagnosis of talaromyces.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

200 participants in 2 patient groups

HIV Negative Host talaromyces using Voriconazole

Experimental group

Description:

Voriconazole On the first day, 6 mg/kg bid was given, and then 4 mg/kg bid was given intravenously for 6 days, and then oral voriconazole 200 mg bid was administered to maintain treatment for at least 6 months.

Treatment:

Drug: Voriconazole

HIV Negative talaromyces AMB Sequential Itraconazole

Experimental group

Description:

Amphotericin B (AMB) sequential itraconazole group (intravenous amphotericin, dose 0.7 - 1.0 mg / kg / d, 14 days, then changed oral itraconazole 200 mg bid for 10 weeks, after which 100 mg bid maintenance Until cluster of differentiation 4 (CD4+ T) cells are greater than 100 cells/L for at least 6 months

Treatment:

Drug: Voriconazole