Cryptococcal MeningitisPhase 2/3ACACIANCT03945448
Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia
A Phase 2/3 study testing Single dose liposomal Amphotericin and Fluconazole and Fluconazole in people with Cryptococcal Meningitis, run by Makerere University at 1 site in Uganda.
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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Cryptococcal Meningitis
- What is being tested?
- Single dose liposomal Amphotericin and Fluconazole and Fluconazole
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 356 participants
- Where
- 1 siteUganda
- Study dates
- 20 Jun 2019to Aug 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda1 site, 1 recruiting
- Recruiting
infectious Disease Institute Kampala,Uganda
Kampala
DAVID MEYA, PhD, +256 772 543 730, david.meya@gmail.com
ELIZABETH NALINTYA, MPH, +256 771 321 617, enalintya@idi.co.ug
About this study
Official title: Evaluation of CrAg Screening With Enhanced Antifungal Therapy for Asymptomatic CrAg+ Persons
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.
- Conditions
- Cryptococcal Meningitis
- Being tested
- Single dose liposomal Amphotericin and Fluconazole, Fluconazole
- Medical subject headings
- Meningitis, Cryptococcal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single dose liposomal Amphotericin and FluconazoleDrug
Also called AMBISOME and fluconazole
Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months.
FluconazoleDrug
Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Fluconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 weeks
Secondary outcomes (4)
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.
Measured: within two weeks of enrollment
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.
Measured: 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.
what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes.
Measured: 24 weeks
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start20 Jun 2019
- Primary completionJun 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cryptococcal MeningitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 356 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota, Gilead Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03945448
- Sponsor's protocol ID
- ST/225/2018
- Acronym
- ACACIA
- Status last verified
- Apr 2026
- First submitted
- 12 Mar 2019
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39044381
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of CrAg Screening With Enhanced Antifungal Therapy for Asymptomatic CrAg+ Persons
- ClinicalTrials.gov ID
- NCT03945448
- Acronym / sponsor ID
- ACACIA / ST/225/2018
- Conditions
- Cryptococcal Meningitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 356 participants (estimated)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- University of Minnesota, Gilead Sciences
- Study start
- 20 Jun 2019 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 10 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single dose liposomal Amphotericin and fluconazole | Experimental | Drug: Single dose liposomal Amphotericin and FluconazoleExperimental: 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) | Active comparator | Drug: FluconazoleStandard of care pre-emptive treatment fluconazole 800mg for two weeks ,400mg for 8 weeks and 200mg upto 6 months |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single dose liposomal Amphotericin and FluconazoleAlso: AMBISOME and fluconazoleIntravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months. | Drug | Single dose liposomal Amphotericin and fluconazole |
| FluconazoleFluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months | Drug | fluconazole (standard of care) |
Primary outcome
Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm.
Time frame: 24 weeks
Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone
4 secondary outcomes
Number of grade 3 to 5 clinical adverse events or serious adverse events
Time frame: within two weeks of enrollment
Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale
Time frame: 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.
Time frame: 24 weeks
Number of patients that will survive in the 24-week period.
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Derived from this study: PubMed 39044381Meya 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.
- Individual participant dataSharing planned: No
Related trials for Cryptococcal Meningitis
RecruitingObservational study
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Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
Not yet recruitingPhase 3
Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers
Cryptococcal Antigenemia, HIV-1-infection
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Single dose liposomal Amphotericin and Fluconazole and Fluconazole in people with Cryptococcal Meningitis, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact DAVID MEYA, PhD (+256 772 543 730, david.meya@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03945448, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.