Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

Phase 2

Recruiting

• Conditions: Cryptococcal Meningitis
• Interventions: Drug: Single dose liposomal Amphotericin and Fluconazole; Drug: Fluconazole

• Registration Number: NCT03945448
• Lead Sponsor: Makerere University

Brief Summary

This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda.

Patients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg/kg) in addition to standard of care fluconazole therapy.

How the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-05-08
• Study First Posted: 2019-05-10
• Study Start: 2019-06-20
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-11
• Last Update Posted: 2023-04-12
• Primary Completion: 2027-10
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 356

Inclusion Criteria

• HIV-1 infection
• Age > or equal to15 years
• Ability and willingness to give informed consent.
• Plasma/Serum cryptococcal antigen (CRAG)+ with a titer 1:160 or greater

Exclusion Criteria

• Cannot or unlikely to attend regular clinic visits
• History of cryptococcal infection
• Symptomatic meningitis (confirmed by CSF CRAG+)
• >14 days of fluconazole therapy
• Pregnancy (confirmed by urinary or serum pregnancy test)
• Current breastfeeding
• Known allergy to amphotericin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single dose liposomal Amphotericin and fluconazole	Single dose liposomal Amphotericin and Fluconazole	Experimental: Single dose Ambisome 10mg/kg and Fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months. (standard of care therapy)
fluconazole (standard of care)	Fluconazole	Standard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months

Primary Outcome Measures

Name	Time	Method
Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm.	24 weeks	Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone

Secondary Outcome Measures

Name	Time	Method
Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale	within two weeks of enrollment	Abnormal laboratory findings that meet the DAIDS categorization of grade 3 and 4.
Number of grade 3 to 5 clinical adverse events or serious adverse events	within two weeks of enrollment	Symptoms causing inability to perform social and functional activities and potentially life threatening symptoms requiring intervention or hospitalization.
Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy.	24 weeks	what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes.
Number of patients that will survive in the 24-week period.	24 weeks	How many patients will be alive at 24 weeks when the two arms are compared.

Trial Locations

Locations (1)

infectious Disease Institute Kampala,Uganda; 🇺🇬 Kampala, Uganda