Clinical Effectiveness and Safety of Amphotericin B With Flucytosine-Fluconazole Therapy for Cryptococcal Meningitis

Overview

To study the clinical effectiveness and safety of amphotericin B with flucytosine-fluconazole therapy for cryptococcal meningitis in patients with HIV infection.

Full Title of Study: “Clinical Effectiveness and Safety of Amphotericin B With Flucytosine-Fluconazole Therapy for Cryptococcal Meningitis in Patients With HIV Infection”

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective
• Study Primary Completion Date: March 30, 2022

Detailed Description

Cryptococcal meningitis is an AIDS-defining illness mostly caused by the fungus, Cryptococcus neoformans. In high-income countries, the use of amphotericin B in combination with a more expensive drug, flucytosine, is most effective for the management of cryptococcal meningitis; but access to flucytosine is severely limited in middle and low-income countries. In Myanmar, currently recommended regimen for cryptococcal meningitis are combination of amphotericin B with fluconazole. Although amphotericin plus flucytosine followed by fluconazole therapy is the currently preferred regimen in WHO treatment guidelines, it is not still commonly used in Myanmar clinical practice because of its limited availability. Therefore, the data regarding tolerability and clinical effectiveness of flucytosine are unavailable for Myanmar patients. Although trials were carried out for investigating the effectiveness of flucytosine in the HIV population of Africa, the variability in drug response can occur in Myanmar patients due to the racial and genetic differences and whether it is effective and safe for Myanmar people is a great curiosity question for clinicians and healthcare workers. In Myanmar, amphotericin plus flucytosine followed by fluconazole regimen will be supplied by National AIDS Program (NAP) and indicated in 2020. Thus, the documents for effectiveness and safety profile need to be established. This is the reason that the effectiveness and safety of amphotericin B with flucytosine and fluconazole combination therapy should be studied. From this study, it can provide information to physicians regarding the effectiveness as well as safety of those drugs in the management of cryptococcal meningitis in HIV patients.

Interventions

• Drug: Amphotericin B 1 mg/kg 1 week & Flucytosine 100 mg/kg 1 week followed by Fluconazole 1200 mg/day 1 week
  • To study the clinical effectiveness and safety of amphotericin B with flucytosine-fluconazole therapy for cryptococcal meningitis in patients with HIV infection.

Arms, Groups and Cohorts

• Amphotericin B,Flucytosine, Fluconazole
  • Amphotericin B 1 mg/kg 1 week & Flucytosine 100 mg/kg 1 week followed by Fluconazole 1200 mg/day 1 week

Clinical Trial Outcome Measures

Primary Measures

• Clinical effectiveness
  • Time Frame: 14 days (day1 to day 14)
  • To describe the clinical effectiveness of amphotericin B with flucytosine-fluconazole combination therapy by assessing clinical parameters (presence of headache, fever, convulsion, abnormal mental status and death) at day 1, day 7 and day 14 To determine the severity of headache before and after treatment by numerical rating scale
• Clinical safety
  • Time Frame: 14 days (day1 to day 14)
  • 3. . To describe the clinical safety of amphotericin B with flucytosine-fluconazole combination therapy by assessing hematological and biochemical parameters (hemoglobin, neutrophil, platelet, ALT, AST, serum creatinine and serum potassium level ) by DAIDS grading at baseline, day 7 and day 14

Secondary Measures

• back-ground characteristics of patients
  • Time Frame: 14 days (day1 to day 14)
  • 4. To find out the back-ground characteristics of patients (age,gender) with HIV-associated cryptococcal meningitis

Participating in This Clinical Trial

Inclusion Criteria

1. Patients with HIV-associated cryptococcal meningitis, admitted to inpatient department of SHW, SHM, SHT, YGH, NOGTH and IGH during the study period 2. Patients of both sexes 3. Age above 14 years 4. Patients or caregivers who will give informed consent to participate in this study

Gender Eligibility: All

Minimum Age: 14 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of Pharmacy, Yangon
• Provider of Information About this Clinical Study
  • Principal Investigator: Ms. Zin Win May, Principal Investigator, Clinical effectiveness and safety of Amphotericin B with Flucytosine-Fluconazole therapy for Cryptococcal meningitis in patients with HIV infection – University of Pharmacy, Yangon
• Overall Official(s)
  • zin win may, B.Pharm, Principal Investigator, Specialist Hospital Thakeyta