Three Induction Treatments on Cryptococcal Meningitis

Early Phase 1

• Conditions: Cryptococcal Meningitis; HIV/AIDS
• Interventions: Drug: Voriconazole 200mg; Drug: Amphotericin B-deoxycholate (0.7-1.0mg/kg/d); Drug: amphotericin B deoxycholate (0.4-0.5mg/kg/d)

• Registration Number: NCT04072640
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

Three induction treatment strategies \[ voriconazole +5FC vs. amphotericin deoxycholate (0.4-0.5 mg/kg/d)+5FC vs. amphotericin deoxycholate (0.7-1.0 mg/kg/d)+5FC \] for HIV-infected patients with cryptococcal meningitis were compared.

Detailed Description

HIV-associated cryptococcal meningitis were randomly allocated into three induction treatment as follow: 1) 14 days of voriconazole 200mg bid +5FC, 2) 28 days of amphotericin deoxycholate (0.4-0.5 mg/kg/d) +5FC ; 3）14 days of deoxycholate (0.7-1 mg/kg/d) +5FC). After induction treatment were finished, all groups switched into fluconazole(400mg/d) for two-month consolidation treatment. 14-day early fungicidal rate, 90-day mortality, side effects , and tolerances were compared between three groups.

Study Timeline

• Study First Submitted: 2019-06-09
• Study First Submitted QC: 2019-08-27
• Study First Posted: 2019-08-28
• Status Verified: 2021-01
• Study Start: 2021-01-25
• Last Update Submitted: 2021-01-31
• Last Update Posted: 2021-02-02
• Primary Completion: 2022-07-31
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Clinical diagnosis of HIV infection;
2. newly diagnosed Cryptococcal Meningitis by positive India ink staining or culture result, or both in cerebrospinal fluid (CSF);
3. Anti-viral treatment naïve patients
4. anti-fungal treatment naïve patients

Exclusion Criteria

1. hepatitis virus co-infection;
2. liver cirrhosis;
3. congestive heart failure;
4. chronic renal disorders;
5. chronic obstructive pulmonary disease (COPD);
6. Tuberculosis co-infection;
7. malignances
8. severe mental and neurological diseases
9. Women during pregnancy and lactation
10. intraveneous drug user (IDU)
11. patients with follow abnormal test results:hemoglobin < 6 g/dl, white blood cell count < 2000 / μl, neutrophil count < 1000 / μl, platelet count < 75000 / μl, blood amylase > 3 times normal level Upper limit, serum creatinine > 1.5 times normal upper limit, aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase > 3 times normal upper limit, total bilirubin > 2 times normal upper limit
12. patients who are unwilling to anticipate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
voriconazole treatment	Voriconazole 200mg	induction treatment with Voriconazole 200mg bid (IV) + 5FC (100mg/kg/d) for 14 days, consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d
amphotericin treatment (0.7-1.0mg/kg/d)	Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)	Induction treatment with amphotericin B 0.7-1.0mg/kg/d + 5FC (100mg/kg/d) for 14 days,consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d
amphotericin B treatment (0.4-0.5mg/kg/d)	amphotericin B deoxycholate (0.4-0.5mg/kg/d)	Induction treatment with amphotericin B 0.4-0.5mg/kg/d + 5FC (100mg/kg/d) for 28 days, consolidation treatment with fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d

Primary Outcome Measures

Name	Time	Method
90-day Cryptococcal Meningitis (CM) related mortality	90 days	analysis of 90-day CM-related mortality of patients in three induction treatments

Secondary Outcome Measures

Name	Time	Method
Hypokalemia	0-90 days	To observe the rate of hypokalemia in three groups during antifungal therapy
Early fungicidal rate in Cerebrospinal fluid (CSF)	2 weeks	Comparison of 2-week CSF early fungicidal activity in three induction treatments
anemia	0-90 days	Comparison of the numbers of patients with hemoglobin \<120g/L for male or \<110g/L for female.
creatinine elevation	0-90 days	TO observe the numbers of patients whose creatinine \> 110 mmol/L during antifungal therapy

Trial Locations

Locations (1)

Lijun Xu; 🇨🇳 Zhenjiang, Hangzhou, China