Back to resultsClinical Study of ABCD in the Treatment of Cryptococcal Meningitis
Primary Purpose
Cryptococcal Meningitis
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Amphotericin B Colloidal Dispersion
flucytosine
fluconazole
Sponsored by
About this trial
This is an interventional treatment trial for Cryptococcal Meningitis focused on measuring cryptococcal meningitis, Amphotericin B Colloidal Dispersion, non-HIV patients
Eligibility Criteria
Inclusion Criteria:
- ≥18 years old and ≤70 years old, no gender limitation;
- Diagnosis of cryptococcal meningitis (with or without other cryptococcal lesions) based on CSF culture and/or CSF ink staining smear and/or CSF antigen testing;
- The researcher believes that patients can benefit from participating in this study;
- The subjects voluntarily participated in the study and signed the informed consent.
Exclusion Criteria:
- Patients with other invasive fungal diseases;
- HIV infected patients;
- Patients who received intravenous polyene treatment within the past 6 months;
- Allergic to Amphotericin B Colloidal Dispersion or other ingredients in this product;
- Patients with abnormal liver function [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >＝5 times the upper limit of normal value (ULN) without total bilirubin elevation, or ALT or AST >＝ 3 times ULN with total bilirubin >＝ 1.5 times];
- Patients with impaired renal function (renal function index blood creatinine (Cr) is more than 2 times higher than ULN, or 24-hour urine creatinine clearance rate （Ccr） is less than 50ml/min), or patients requiring/undergoing hemodialysis or peritoneal dialysis;
- Pregnant women, breast-feeding women and women of childbearing age who were unable to take effective contraceptive measures during the study period;
- Conditions considered unsuitable for the study by the investigator, such as concomitancy of severe organ insufficiency, clinically significant laboratory abnormalities, comprehension or compliance problems, etc.
Sites / Locations
- Peking Union Medical College Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ABCD treatment
Arm Description
In this single-arm research, patients were treated with ABCD 3.0-4.0 mg/kg/d (subject to adjustment, maximum dose not exceeding 6.0 mg/kg/d) combined with flucytosine 100 mg/kg/d for induction therapy of cryptococcal meningitis. The course of induction therapy is at least four weeks. Then, patients were treated with Fluconazole (400-600 mg/d) ± flucytosine (100 mg/kg/d) for consolidation therapy for at least 6 weeks.
Outcomes
Primary Outcome Measures
Proportion of patients with complete or partial response at the end of induction therapy
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Secondary Outcome Measures
Proportion of patients with complete or partial response at 4 weeks
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Proportion of patients with complete or partial response at 10 weeks
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Proportion of patients with complete or partial response at the end of consolidation therapy
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Cryptococcus antigen titer
Diachronic changes in antigenic titers of Cryptococcus
Duration of the cryptococcal meningitis
The time from this hospitalization to the end of consolidation therapy.
Adverse events
Incidence and severity of adverse events during treatment, evaluated according to NCI-CTCAE Ver. 5.0.
Full Information
NCT ID
NCT05471063
First Posted
July 1, 2022
Last Updated
July 20, 2022
Sponsor
Peking Union Medical College Hospital
Collaborators
CSPC Ouyi Pharmaceutical Group Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05471063
Brief Title
Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis
Official Title
Clinical Study of Amphotericin B Colloidal Dispersion (ABCD) in the Treatment of Cryptococcal Meningitis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 22, 2022 (Anticipated)
Primary Completion Date
February 28, 2023 (Anticipated)
Study Completion Date
April 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
CSPC Ouyi Pharmaceutical Group Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
To evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients at week 4, the end of induction therapy, week 10 and the end of consolidation therapy.
Detailed Description
This study is a multi-center, single-arm clinical study. The objective is to evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients. Qualified subjects shall receive cryptococcus induction therapy with ABCD combined with flucytosine for at least 4 weeks, or termination of treatment early at the investigator's discretion. Efficacy and safety are followed up at week 4 (day 28), the end of induction therapy, week 10 (day 70) and the end of consolidation therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis
Keywords
cryptococcal meningitis, Amphotericin B Colloidal Dispersion, non-HIV patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ABCD treatment
Arm Type
Experimental
Arm Description
In this single-arm research, patients were treated with ABCD 3.0-4.0 mg/kg/d (subject to adjustment, maximum dose not exceeding 6.0 mg/kg/d) combined with flucytosine 100 mg/kg/d for induction therapy of cryptococcal meningitis. The course of induction therapy is at least four weeks. Then, patients were treated with Fluconazole (400-600 mg/d) ± flucytosine (100 mg/kg/d) for consolidation therapy for at least 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Amphotericin B Colloidal Dispersion
Other Intervention Name(s)
Amphotericin B Cholesteryl Sulfate Complex for Injection
Intervention Description
Amphotericin B Colloidal Dispersion 3.0-4.0 mg/kg/d (subject to adjustment, maximum dose not exceeding 6.0 mg/kg/d) . The course of induction therapy is at least four weeks.
Intervention Type
Drug
Intervention Name(s)
flucytosine
Other Intervention Name(s)
fluorocytosine
Intervention Description
Flucytosine 100 mg/kg/d for induction therapy and consolidation therapy of cryptococcal meningitis. The course of induction therapy is at least four weeks, and consolidation therapy for at least 6 weeks.
Intervention Type
Drug
Intervention Name(s)
fluconazole
Other Intervention Name(s)
Diflucan
Intervention Description
Fluconazole (400-600 mg/d) for consolidation therapy for at least 6 weeks.
Primary Outcome Measure Information:
Title
Proportion of patients with complete or partial response at the end of induction therapy
Description
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Time Frame
From enrollment to the end of induction therapy (about 4-6 weeks)
Secondary Outcome Measure Information:
Title
Proportion of patients with complete or partial response at 4 weeks
Description
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Time Frame
At the 4 weeks of treatment
Title
Proportion of patients with complete or partial response at 10 weeks
Description
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Time Frame
At the 10 weeks of treatment
Title
Proportion of patients with complete or partial response at the end of consolidation therapy
Description
Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.
Time Frame
At the end of the consolidation therapy (about 12 weeks)
Title
Cryptococcus antigen titer
Description
Diachronic changes in antigenic titers of Cryptococcus
Time Frame
1,2,3,4,10 weeks
Title
Duration of the cryptococcal meningitis
Description
The time from this hospitalization to the end of consolidation therapy.
Time Frame
At the end of the consolidation therapy (about 12 weeks)
Title
Adverse events
Description
Incidence and severity of adverse events during treatment, evaluated according to NCI-CTCAE Ver. 5.0.
Time Frame
about 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥18 years old and ≤70 years old, no gender limitation;
Diagnosis of cryptococcal meningitis (with or without other cryptococcal lesions) based on CSF culture and/or CSF ink staining smear and/or CSF antigen testing;
The researcher believes that patients can benefit from participating in this study;
The subjects voluntarily participated in the study and signed the informed consent.
Exclusion Criteria:
Patients with other invasive fungal diseases;
HIV infected patients;
Patients who received intravenous polyene treatment within the past 6 months;
Allergic to Amphotericin B Colloidal Dispersion or other ingredients in this product;
Patients with abnormal liver function [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >＝5 times the upper limit of normal value (ULN) without total bilirubin elevation, or ALT or AST >＝ 3 times ULN with total bilirubin >＝ 1.5 times];
Patients with impaired renal function (renal function index blood creatinine (Cr) is more than 2 times higher than ULN, or 24-hour urine creatinine clearance rate （Ccr） is less than 50ml/min), or patients requiring/undergoing hemodialysis or peritoneal dialysis;
Pregnant women, breast-feeding women and women of childbearing age who were unable to take effective contraceptive measures during the study period;
Conditions considered unsuitable for the study by the investigator, such as concomitancy of severe organ insufficiency, clinically significant laboratory abnormalities, comprehension or compliance problems, etc.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Cao, PhD
Phone
010-69156114
Email
wcao_pumch@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Taisheng Li, PhD
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Cao, PhD
Phone
010-69156114
Email
wcao_pumch@163.com
First Name & Middle Initial & Last Name & Degree
Taisheng Li, PhD
First Name & Middle Initial & Last Name & Degree
Wei Cao, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis
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