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

Clinical Effectiveness and Safety of Amphotericin B With Flucytosine-Fluconazole Therapy for Cryptococcal Meningitis in Patients With HIV Infection

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

Study Overview

• Status: Completed
• Conditions: Cryptococcal Meningitis
• Intervention / Treatment: Drug: Amphotericin B 1 mg/kg 1 week & Flucytosine 100 mg/kg 1 week followed by Fluconazole 1200 mg/day 1 week

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.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Myanmar
  • Yangon, Myanmar, 11181
    • Specialist hospital Mingalardon,Thakeyta and Waibargi,Yangon General Hospital,Insein General Hospital, North Oakalapa General and Teaching Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to SHW, SHM, SHT, YGH, NOGTH and IGH with HIV-associated cryptococcal meningitis who will be treated with amphotericin + flucytosine + fluconazole induction regimen.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical effectiveness	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	14 days (day1 to day 14)
Clinical safety	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	14 days (day1 to day 14)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Pharmacy, Yangon
• Investigators: Principal Investigator: zin win may, B.Pharm, Specialist Hospital Thakeyta

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): April 20, 2022

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Bacterial Infections and Mycoses; Mycoses; Meningitis, Fungal; Central Nervous System Fungal Infections; Cryptococcosis; Meningitis; Meningitis, Cryptococcal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole; Flucytosine; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: 122020