Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis

NCT05471063 | Unknown

• 1 other identifier: CSPC-ABCD-K09
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Cryptococcal Meningitis

Keywords

cryptococcal meningitis; Amphotericin B Colloidal Dispersion; non-HIV patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Proportion of patients with complete or partial response at 4 weeks

  At the 4 weeks of treatment

• Proportion of patients with complete or partial response at 10 weeks

  At the 10 weeks of treatment

• Proportion of patients with complete or partial response at the end of consolidation therapy

  At the end of the consolidation therapy (about 12 weeks)

• Cryptococcus antigen titer

  1,2,3,4,10 weeks

• Duration of the cryptococcal meningitis

  At the end of the consolidation therapy (about 12 weeks)

Study Arms (1)

ABCD treatment

EXPERIMENTAL

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.

Drug: Amphotericin B Colloidal Dispersion; Drug: flucytosine; Drug: fluconazole

Interventions

Amphotericin B Colloidal Dispersion DRUG

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.

Also known as: Amphotericin B Cholesteryl Sulfate Complex for Injection

ABCD treatment

flucytosine DRUG

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.

Also known as: fluorocytosine

ABCD treatment

fluconazole DRUG

Fluconazole (400-600 mg/d) for consolidation therapy for at least 6 weeks.

Also known as: Diflucan

ABCD treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• CSPC Ouyi Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Meningitis, Cryptococcal

Interventions

Amphotericin B; Injections; Flucytosine; Fluconazole

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Cryptococcosis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Azoles

Study Officials

• Taisheng Li, PhD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Cao, PhD

CONTACT

010-69156114; wcao_pumch@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director in department of Infectious Diseases

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 22, 2022
• Study Start: August 22, 2022
• Primary Completion: February 28, 2023
• Study Completion: April 30, 2023
• Last Updated: July 22, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)