Clinical Trials

MainTitle

Three Induction Treatments on Cryptococcal Meningitis (TITOC)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified June 2019 by First Affiliated Hospital of Zhejiang University

Sponsor
First Affiliated Hospital of Zhejiang University

Collaborator
Wenzhou Central Hospital

Information provided by (Responsible Party)
First Affiliated Hospital of Zhejiang University
ClinicalTrials.gov Identifier
NCT04072640

First received: June 9, 2019
Last updated: September 2, 2019
Last Verified: June 2019
History of Changes
Purpose

Purpose

Three induction treatment strategies [ voriconazole +5FC vs. amphotericin deoxycholate (0.4-0.5 mg/kg/d)+5FC vs. amphotericin deoxycholate (0.7-1.0 mg/kg/d)+5FC ] for HIV-infected patients with cryptococcal meningitis were compared.

Condition Intervention Phase
Cryptococcal Meningitis
HIV/AIDS

Drug : Voriconazole 200mg
Drug : amphotericin B deoxycholate (0.4-0.5mg/kg/d)
Drug : Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)
Early Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect and Safety of Three Initial Introduction Treatments on HIV-infected Patients With Cryptococcal Meningitis: A Multi-center, Random and Prospective Study

Further study details as provided by First Affiliated Hospital of Zhejiang University:

Primary Outcome Measures

  • 90-day Cryptococcal Meningitis (CM) related mortality [ Time Frame: 90 days ]
    analysis of 90-day CM-related mortality of patients in three induction treatments
Secondary Outcome Measures:
  • Early fungicidal rate in Cerebrospinal fluid (CSF) [ Time Frame: 2 weeks ]
    Comparison of 2-week CSF early fungicidal activity in three induction treatments
  • creatinine elevation [ Time Frame: 0-90 days ]
    TO observe the numbers of patients whose creatinine > 110 mmol/L during antifungal therapy
  • Hypokalemia [ Time Frame: 0-90 days ]
    To observe the rate of hypokalemia in three groups during antifungal therapy
  • anemia [ Time Frame: 0-90 days ]
    Comparison of the numbers of patients with hemoglobin <120g/L for male or <110g/L for female.

Estimated Enrollment: 120
Anticipated Study Start Date: January 1, 2020
Estimated Study Completion Date: December 1, 2022
Estimated Primary Completion Date: July 31, 2022 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: voriconazole treatment
induction treatment with Voriconazole 200mg bid (IV) + 5FC (100mg/kg/d) for 14 days, consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d
Drug: Voriconazole 200mg

Induction treatment with voriconazole( 400mg/d)+5FC (100mg/kg/d) for 14 days;

Other Name: Voriconazole for Cryptococcus
Active Comparator: amphotericin treatment (0.7-1.0mg/kg/d)
Induction treatment with amphotericin B 0.7-1.0mg/kg/d + 5FC (100mg/kg/d) for 14 days,consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d
Drug: Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)

Induction treatment with 0.7-1.0mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 14 days

Other Name: standard Amphotericin B-deoxycholate for Cryptococcus
Experimental: amphotericin B treatment (0.4-0.5mg/kg/d)
Induction treatment with amphotericin B 0.4-0.5mg/kg/d + 5FC (100mg/kg/d) for 28 days, consolidation treatment with fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d
Drug: amphotericin B deoxycholate (0.4-0.5mg/kg/d)

Induction treatment with 0.4-0.5mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 28 days

Other Name: low dose and long course of Amphotericin B-deoxycholate

Detailed Description:

HIV-associated cryptococcal meningitis were randomly allocated into three induction treatment as follow: 1) 14 days of voriconazole 200mg bid +5FC, 2) 28 days of amphotericin deoxycholate (0.4-0.5 mg/kg/d) +5FC ; 3)14 days of deoxycholate (0.7-1 mg/kg/d) +5FC). After induction treatment were finished, all groups switched into fluconazole(400mg/d) for two-month consolidation treatment. 14-day early fungicidal rate, 90-day mortality, side effects , and tolerances were compared between three groups.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. Clinical diagnosis of HIV infection;
    2. newly diagnosed Cryptococcal Meningitis by positive India ink staining or culture result, or both in cerebrospinal fluid (CSF);
    3. Anti-viral treatment naïve patients
    4. anti-fungal treatment naïve patients


Exclusion Criteria:
    1. hepatitis virus co-infection;
    2. liver cirrhosis;
    3. congestive heart failure;
    4. chronic renal disorders;
    5. chronic obstructive pulmonary disease (COPD);
    6. Tuberculosis co-infection;
    7. malignances
    8. severe mental and neurological diseases
    9. Women during pregnancy and lactation
    10. intraveneous drug user (IDU)
    11. patients with follow abnormal test results:hemoglobin < 6 g/dl, white blood cell count < 2000 / μl, neutrophil count < 1000 / μl, platelet count < 75000 / μl, blood amylase > 3 times normal level Upper limit, serum creatinine > 1.5 times normal upper limit, aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase > 3 times normal upper limit, total bilirubin > 2 times normal upper limit
    12. patients who are unwilling to anticipate.

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: NCT04072640

Contacts

Contact:   Lijun Xu, PH.D 0086-571-87236417 xulijun1976@zju.edu.cn
Contact:   Ying Huang 0086-571-87236437 hyboby@zju.edu.cn

Sponsors and Collaborators

First Affiliated Hospital of Zhejiang University
Wenzhou Central Hospital

Investigators

Principal Investigator: Lijun Xu, PH.D Zhejiang University
More Information

More Information


Responsible Party: First Affiliated Hospital of Zhejiang University  
ClinicalTrials.gov Identifier: NCT04072640   History of Changes  
Other Study ID Numbers: 2018-014-1  
Study First Received: June 9, 2019  
Last Updated: September 2, 2019  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: No  

Keywords provided by First Affiliated Hospital of Zhejiang University:

Voriconazole;amphotericin ;cryptococcal meningitis

Additional relevant MeSH terms:
Meningitis, Cryptococcal
Meningitis
Voriconazole
Amphotericin B
Liposomal amphotericin B
Amphotericin B, deoxycholate drug combination
Deoxycholic Acid

ClinicalTrials.gov processed this data on October 15, 2019
This information is provided by ClinicalTrials.gov.