Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis

Cryptococcal Meningitis Clinical Trial

Official title:

Clinical Study of Amphotericin B Colloidal Dispersion (ABCD) in the Treatment of Cryptococcal Meningitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05471063
• Other study ID #: CSPC-ABCD-K09
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 22, 2022
• Est. completion date: April 30, 2023

Study information

• Verified date: July 2022
• Source: Peking Union Medical College Hospital
• Contact: Wei Cao, PhD
• Phone: 010-69156114
• Email: wcao_pumch[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: April 30, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Amphotericin 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.
• flucytosine
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.
• fluconazole
Fluconazole (400-600 mg/d) for consolidation therapy for at least 6 weeks.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	CSPC Ouyi Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From enrollment to the end of induction therapy (about 4-6 weeks)
Secondary	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.	At the 4 weeks of treatment
Secondary	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.	At the 10 weeks of treatment
Secondary	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.	At the end of the consolidation therapy (about 12 weeks)
Secondary	Cryptococcus antigen titer	Diachronic changes in antigenic titers of Cryptococcus	1,2,3,4,10 weeks
Secondary	Duration of the cryptococcal meningitis	The time from this hospitalization to the end of consolidation therapy.	At the end of the consolidation therapy (about 12 weeks)
Secondary	Adverse events	Incidence and severity of adverse events during treatment, evaluated according to NCI-CTCAE Ver. 5.0.	about 12 weeks