Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

Cryptococcal Meningitis Clinical Trial

— ACACIA  

Official title:

Evaluation of CrAg Screening With Enhanced Antifungal Therapy for Asymptomatic CrAg+ Persons

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03945448
• Other study ID #: ST/225/2018
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 20, 2019
• Est. completion date: April 2028

Study information

• Verified date: April 2023
• Source: Makerere University
• Contact: DAVID MEYA, PhD
• Phone: +256 772 543 730
• Email: david.meya[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 356
• Est. completion date: April 2028
• Est. primary completion date: October 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Single dose liposomal Amphotericin and Fluconazole
Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months.
• Fluconazole
Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months

Locations

Country	Name	City	State
Uganda	infectious Disease Institute Kampala,Uganda	Kampala

Sponsors (3)

Lead Sponsor	Collaborator
Makerere University	Gilead Sciences, University of Minnesota

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm.	Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone	24 weeks
Secondary	Number of grade 3 to 5 clinical adverse events or serious adverse events	Symptoms causing inability to perform social and functional activities and potentially life threatening symptoms requiring intervention or hospitalization.	within two weeks of enrollment
Secondary	Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale	Abnormal laboratory findings that meet the DAIDS categorization of grade 3 and 4.	within two weeks of enrollment
Secondary	Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy.	what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes.	24 weeks
Secondary	Number of patients that will survive in the 24-week period.	How many patients will be alive at 24 weeks when the two arms are compared.	24 weeks