search
Back to results

Three Induction Treatments on Cryptococcal Meningitis (TITOC)

Primary Purpose

Cryptococcal Meningitis, HIV/AIDS

Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Voriconazole 200mg
amphotericin B deoxycholate (0.4-0.5mg/kg/d)
Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)
Sponsored by
First Affiliated Hospital of Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryptococcal Meningitis focused on measuring Voriconazole;amphotericin ;cryptococcal meningitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Lijun Xu

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

voriconazole treatment

amphotericin treatment (0.7-1.0mg/kg/d)

amphotericin B treatment (0.4-0.5mg/kg/d)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

90-day Cryptococcal Meningitis (CM) related mortality
analysis of 90-day CM-related mortality of patients in three induction treatments

Secondary Outcome Measures

Early fungicidal rate in Cerebrospinal fluid (CSF)
Comparison of 2-week CSF early fungicidal activity in three induction treatments
creatinine elevation
TO observe the numbers of patients whose creatinine > 110 mmol/L during antifungal therapy
Hypokalemia
To observe the rate of hypokalemia in three groups during antifungal therapy
anemia
Comparison of the numbers of patients with hemoglobin <120g/L for male or <110g/L for female.

Full Information

First Posted
June 9, 2019
Last Updated
January 31, 2021
Sponsor
First Affiliated Hospital of Zhejiang University
Collaborators
Wenzhou Central Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT04072640
Brief Title
Three Induction Treatments on Cryptococcal Meningitis
Acronym
TITOC
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 25, 2021 (Actual)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
December 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First Affiliated Hospital of Zhejiang University
Collaborators
Wenzhou Central Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis, HIV/AIDS
Keywords
Voriconazole;amphotericin ;cryptococcal meningitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
voriconazole treatment
Arm Type
Experimental
Arm Description
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
Arm Title
amphotericin treatment (0.7-1.0mg/kg/d)
Arm Type
Active Comparator
Arm Description
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
Arm Title
amphotericin B treatment (0.4-0.5mg/kg/d)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Voriconazole 200mg
Other Intervention Name(s)
Voriconazole for Cryptococcus
Intervention Description
Induction treatment with voriconazole( 400mg/d)+5FC (100mg/kg/d) for 14 days;
Intervention Type
Drug
Intervention Name(s)
amphotericin B deoxycholate (0.4-0.5mg/kg/d)
Other Intervention Name(s)
low dose and long course of Amphotericin B-deoxycholate
Intervention Description
Induction treatment with 0.4-0.5mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 28 days
Intervention Type
Drug
Intervention Name(s)
Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)
Other Intervention Name(s)
standard Amphotericin B-deoxycholate for Cryptococcus
Intervention Description
Induction treatment with 0.7-1.0mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 14 days
Primary Outcome Measure Information:
Title
90-day Cryptococcal Meningitis (CM) related mortality
Description
analysis of 90-day CM-related mortality of patients in three induction treatments
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Early fungicidal rate in Cerebrospinal fluid (CSF)
Description
Comparison of 2-week CSF early fungicidal activity in three induction treatments
Time Frame
2 weeks
Title
creatinine elevation
Description
TO observe the numbers of patients whose creatinine > 110 mmol/L during antifungal therapy
Time Frame
0-90 days
Title
Hypokalemia
Description
To observe the rate of hypokalemia in three groups during antifungal therapy
Time Frame
0-90 days
Title
anemia
Description
Comparison of the numbers of patients with hemoglobin <120g/L for male or <110g/L for female.
Time Frame
0-90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical diagnosis of HIV infection; newly diagnosed Cryptococcal Meningitis by positive India ink staining or culture result, or both in cerebrospinal fluid (CSF); Anti-viral treatment naïve patients anti-fungal treatment naïve patients Exclusion Criteria: hepatitis virus co-infection; liver cirrhosis; congestive heart failure; chronic renal disorders; chronic obstructive pulmonary disease (COPD); Tuberculosis co-infection; malignances severe mental and neurological diseases Women during pregnancy and lactation intraveneous drug user (IDU) 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 patients who are unwilling to anticipate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lijun Xu, PH.D
Organizational Affiliation
Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lijun Xu
City
Zhenjiang
State/Province
Hangzhou
ZIP/Postal Code
310020
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
12 months after study finished
IPD Sharing Time Frame
12 months
IPD Sharing Access Criteria
Qualified researchers may submit a request containing the research objectives, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s).

Learn more about this trial

Three Induction Treatments on Cryptococcal Meningitis

We'll reach out to this number within 24 hrs