Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis

Not Applicable

• Conditions: Cryptococcal Meningitis
• Interventions: Drug: Amphotericin B Colloidal Dispersion; Drug: flucytosine; Drug: fluconazole

• Registration Number: NCT05471063
• Lead Sponsor: Peking Union Medical College Hospital

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.

Study Timeline

• Status Verified: 2022-07
• Study First Submitted: 2022-07-01
• Study First Submitted QC: 2022-07-20
• Last Update Submitted: 2022-07-20
• Study First Posted: 2022-07-22
• Last Update Posted: 2022-07-22
• Study Start: 2022-08-22
• Primary Completion: 2023-02-28
• Study Completion: 2023-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ABCD treatment	Amphotericin B Colloidal Dispersion	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.
ABCD treatment	flucytosine	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.
ABCD treatment	fluconazole	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
Cryptococcus antigen titer	1,2,3,4,10 weeks	Diachronic changes in antigenic titers of Cryptococcus
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.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China