Cryptococcal Meningitis
Conditions
Keywords
cryptococcal meningitis, Amphotericin B Colloidal Dispersion, non-HIV patients
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.
Interventions
DRUGAmphotericin B Colloidal Dispersion
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.
DRUGflucytosine
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.
DRUGfluconazole
Fluconazole (400-600 mg/d) for consolidation therapy for at least 6 weeks.
Sponsors
CSPC Ouyi Pharmaceutical Group Co., Ltd.
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with complete or partial response at the end of induction therapy | From enrollment to the end of induction therapy (about 4-6 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with complete or partial response at 10 weeks | At the 10 weeks of treatment | 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 | At the end of the consolidation therapy (about 12 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 4 weeks | At the 4 weeks of treatment | 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. |
| Duration of the cryptococcal meningitis | At the end of the consolidation therapy (about 12 weeks) | The time from this hospitalization to the end of consolidation therapy. |
| Adverse events | about 12 weeks | Incidence and severity of adverse events during treatment, evaluated according to NCI-CTCAE Ver. 5.0. |
| Cryptococcus antigen titer | 1,2,3,4,10 weeks | Diachronic changes in antigenic titers of Cryptococcus |
Countries
China
Contacts
Primary ContactWei Cao, PhD
Outcome results
None listed