Clinical trial NCT03827278: Comparative Study of Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin Sequential Itraconazole Therapy
Official title: Human Immunodeficiency Virus Negative Host Talaromyces Between Voriconazole and Amphotericin B Sequential Itraconazole Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Talaromyces in Human Immunodeficiency Virus Negative
To Compare Voriconazole and Amphotericin Sequential Itraconazole Therapy
To Dynamically Monitor the Anti-Interferon-γ Autoantibodies
Keywords: Talaromyces
voriconazole
Amphotericin Sequential Itraconazole therapy
anti-Interferon-γ autoantibodies
Lead sponsor: Guangxi Medical University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Guangxi Medical University
name: Second Affiliated Hospital of Guangzhou Medical University
name: The Fourth People's Hospital of Nanning
name: Guilin Medical College
name: Nanning Second People's Hospital
First posted: 2019-02-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with all-cause mortality
timeFrame: up to 2 weeks
measure: Number of Participants with all-cause mortality
timeFrame: up to 24 weeks
measure: Number of Participants with Clinical resolution of talaromyces
timeFrame: 3 days
measure: Number of Participants with Early fungicidal activity
timeFrame: up to 2 weeks
measure: Number of Participants with Relapse of talaromyces
timeFrame: an average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Nanning
country: China
facility: Guangxi Medical University
state: Guangxi
Study officials:
References:
citation: 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.