Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified February 2019 by Qiu Ye, Guangxi Medical University

Sponsor
Guangxi Medical University

Collaborator
First Affiliated Hospital of Guangxi Medical University
Second Affiliated Hospital of Guangzhou Medical University
The Fourth People’s Hospital of Nanning
Guilin Medical College
Nanning Second People's Hospital

Information provided by (Responsible Party)
Qiu Ye, Guangxi Medical University

ClinicalTrials.gov Identifier
NCT03827278

First received: January 25, 2019
Last updated: February 2, 2019
Last Verified: February 2019
History of Changes
Purpose

Purpose

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

Drug : Voriconazole

Study Type: Interventional
Study Design: 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

Further study details as provided by Qiu Ye, Guangxi Medical University:

Primary Outcome Measures

  • Number of Participants with all-cause mortality [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Estimated Enrollment: 200
Study Start Date: December 30, 2018
Estimated Study Completion Date: December 30, 2021
Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name:
  • 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 Name:
  • Amphotericin
  • Itraconazole

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 85 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03827278

Locations

China
Guangxi Medical University Recruiting
Nanning, Guangxi, China, 530021
Contact: Ye Qiu, M.D    0771-5356702    yeqiu2013graduated@163.com
Principal Investigator: Jianquan Zhang, Professor
Sub-Investigator: Wen Zen, M.D
Sub-Investigator: Hui Zhang, M.D
Sub-Investigator: Mianluan Pan, M.D
Sub-Investigator: Shudan Tang, M.D
Sub-Investigator: Yanping Tang, M.D
Sub-Investigator: Haiguang Xu, M.D
Sub-Investigator: Jie Huang, M.D
Sub-Investigator: Xin Feng, M.D
Principal Investigator: Ye Qiu, M.D
Sub-Investigator: Haiting Qin, M.D
Sub-Investigator: Minchao Duan, M.D

Sponsors and Collaborators

Guangxi Medical University
First Affiliated Hospital of Guangxi Medical University
Second Affiliated Hospital of Guangzhou Medical University
The Fourth People’s Hospital of Nanning
Guilin Medical College
Nanning Second People's Hospital
More Information

More Information

Additional Information:

Related Info

Responsible Party: Qiu Ye, Clinical Professor, Guangxi Medical University  
ClinicalTrials.gov Identifier: NCT03827278   History of Changes  
Other Study ID Numbers: TSM-AMB-VOR-2018  
Study First Received: January 25, 2019  
Last Updated: February 2, 2019  
Individual Participant Data    
Plan to Share IPD: Undecided  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Qiu Ye, Guangxi Medical University:

Talaromyces
voriconazole
Amphotericin Sequential Itraconazole therapy
anti-Interferon-γ autoantibodies

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Itraconazole
Hydroxyitraconazole
Voriconazole
Amphotericin B
Liposomal amphotericin B

ClinicalTrials.gov processed this data on August 16, 2019
This information is provided by ClinicalTrials.gov.