NCT03945448

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
356

participants targeted

Target at P75+ for phase_2

Timeline
15mo left

Started Jun 2019

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress85%
Jun 2019Aug 2027

First Submitted

Initial submission to the registry

March 12, 2019

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 10, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

June 20, 2019

Completed
8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2027

Last Updated

April 28, 2026

Status Verified

April 1, 2026

Enrollment Period

8 years

First QC Date

March 12, 2019

Last Update Submit

April 27, 2026

Conditions

Cryptococcal Meningitis

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Number of grade 3 to 5 clinical adverse events or serious adverse events

    within two weeks of enrollment

  • Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale

    within two weeks of enrollment

  • Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy.

    24 weeks

  • Number of patients that will survive in the 24-week period.

    24 weeks

Study Arms (2)

Single dose liposomal Amphotericin and fluconazole

EXPERIMENTAL

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)

Drug: Single dose liposomal Amphotericin and Fluconazole

fluconazole (standard of care)

ACTIVE COMPARATOR

Standard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months

Drug: Fluconazole

Interventions

Single dose liposomal Amphotericin and FluconazoleDRUG

Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months.

Also known as: AMBISOME and fluconazole
Single dose liposomal Amphotericin and fluconazole
FluconazoleDRUG

Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months

fluconazole (standard of care)

Eligibility Criteria

Age15 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

infectious Disease Institute Kampala,Uganda

Kampala, Uganda

RECRUITING

Related Publications (1)

  • Meya DB, Nalintya E, Skipper CP, Kirumira P, Ayebare P, Naluyima R, Namuli T, Turya F, Walukaga S, Engen N, Hullsiek KH, Wele A, Dai B, Boulware DR, Rajasingham R. Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With HIV-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen Titers. Clin Infect Dis. 2025 Feb 5;80(1):129-136. doi: 10.1093/cid/ciae266.

    PMID: 39044381DERIVED

MeSH Terms

Conditions

Meningitis, Cryptococcal

Interventions

Amphotericin BFluconazoleliposomal amphotericin B

Condition Hierarchy (Ancestors)

Meningitis, FungalCentral Nervous System Fungal InfectionsMycosesBacterial Infections and MycosesInfectionsCryptococcosisCentral Nervous System InfectionsCentral Nervous System DiseasesNervous System DiseasesMeningitisNeuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

MacrolidesPolyketidesLactonesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Central Study Contacts

DAVID MEYA, PhD

CONTACT

+256 772 543 730david.meya@gmail.com

ELIZABETH NALINTYA, MPH

CONTACT

+256 771 321 617enalintya@idi.co.ug

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2019

First Posted

May 10, 2019

Study Start

June 20, 2019

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

August 1, 2027

Last Updated

April 28, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

UG(1)