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

Sponsor

Guangxi Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03827278

Collaborator

First Affiliated Hospital of Guangxi Medical University (Other), Second Affiliated Hospital of Guangzhou Medical University (Other), The Fourth People's Hospital of Nanning (Other), Guilin Medical College (Other), Nanning Second People's Hospital (Other)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Talaromyces in Human Immunodeficiency Virus Negative To Compare Voriconazole and Amphotericin Sequential Itraconazole Therapy To Dynamically Monitor the Anti-Interferon-γ Autoantibodies	Drug: Voriconazole	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin B Sequential Itraconazole Therapy

Actual Study Start Date :

Dec 30, 2018

Anticipated Primary Completion Date :

Dec 30, 2021

Anticipated Study Completion Date :

Dec 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HIV Negative Host talaromyces using Voriconazole 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.	Drug: Voriconazole 6mg/kg bid, was given on the first day, followed by intravenous 4mg/kg bid for 6 days, followed by oral Valconazole 200mg bid for at least 6 months. Amphotericin B 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 CD4+ T cells are greater than 100 cells/L for at least 6 months Other Names: Amphotericin Itraconazole
Experimental: HIV Negative talaromyces AMB Sequential Itraconazole 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	Drug: Voriconazole 6mg/kg bid, was given on the first day, followed by intravenous 4mg/kg bid for 6 days, followed by oral Valconazole 200mg bid for at least 6 months. Amphotericin B 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 CD4+ T cells are greater than 100 cells/L for at least 6 months Other Names: Amphotericin Itraconazole

Arm

Intervention/Treatment

Experimental: HIV Negative Host talaromyces using Voriconazole

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.

Drug: Voriconazole

6mg/kg bid, was given on the first day, followed by intravenous 4mg/kg bid for 6 days, followed by oral Valconazole 200mg bid for at least 6 months. Amphotericin B 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 CD4+ T cells are greater than 100 cells/L for at least 6 months

Other Names:

Amphotericin

Itraconazole

Experimental: HIV Negative talaromyces AMB Sequential Itraconazole

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

Drug: Voriconazole

Other Names:

Amphotericin

Itraconazole

Outcome Measures

Primary Outcome Measures

Number of Participants with all-cause mortality [up to 2 weeks]
defined as the absolute risk of death from any cause during the first 2 weeks
Number of Participants with all-cause mortality [up to 24 weeks]
defined as the absolute risk of death from any cause during 24 weeks
Number of Participants with Clinical resolution of talaromyces [3 days]
Clinical resolution of talaromyces was defined as a temperature of less than 38°C (100°F) for 3 days, resolution of skin lesions, and tertile blood cultures. Early fungicidal activity was defined as the rate of decline in blood T. marneffei colony forming units (CFUs).
Number of Participants with Early fungicidal activity [up to 2 weeks]
defined as the rate of decline in blood T. marneffei CFUs from sterical blood cultures obtained during the first 2 weeks.
Number of Participants with Relapse of talaromyces [an average of 1 year]
defined as the recurrence of symptoms and a positive fungal culture from any sterile site that led to reinduction of therapy in patients who had achieved clinical resolution.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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