Testing newer antifungal drugs for cryptococcal meningitis in people with HIV
Compares newer antifungal treatments against standard care in adults with fungal meningitis and HIV.
Plain-language title generated from the registry record
Registry title: Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)
Key facts
- Where
- Kampala and Mbarara, UgandaSee the 2 sites
- Phase
- Phase 2/3
AI summary: who the study is looking for
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults living with HIV who have cryptococcal meningitis, a fungal infection of the lining around the brain.
- Age
- 18 years or older
- Sex
- All sexes can join.
- Disease stage
- Meningitis with a positive cryptococcal antigen (CrAg) test in the spinal fluid (CSF).
- Earlier treatment
- People who had 3 or more doses of antifungal treatment for meningitis in the last 30 days cannot join.
- Biomarker or test result
- Positive CSF cryptococcal antigen (CrAg) test.
Main reasons for not taking part
- Cannot take medicine by mouth or by stomach tube
- Receiving chemotherapy or corticosteroids
- Receiving hemodialysis or known liver cirrhosis
- Pregnant or breastfeeding
- Suspected paradoxical immune reconstitution inflammatory syndrome (IRIS)
Read by machine on 9 November 2026.
Where in Uganda
- Infectious Diseases InstituteKampala, UgandaTaking people
- Mbarara University of Science and TechnologyMbarara, UgandaTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- David Boulware
- Trial code
- NCT06666322
- Record updated
- 27 July 2026
- Original description
Cryptococcal meningitis is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in low and middle income countries where the ongoing HIV/AIDS pandemic increases the risk of cryptococcosis among persons living with HIV infection. The combination of amphotericin and flucytosine (5-FC) has been the mainstay of therapy for the initial management of cryptococcal meningitis for 4 decades. Indeed, the effective delivery of these first line therapy in Africa can lower mortality to 25%. However, several challenges exist. First, even while 5-FC is included on the WHO list of essential medicines, the availability of 5-FC worldwide is limited. Second, liposomal amphotericin (Ambisome ®) is currently available from a single source supplier, creating risk. Third, current therapies have substantial toxicity. Lastly, with widespread agricultural fungicide use of azoles, the median fluconazole minimum inhibitory concentration (MIC50 ) for Cryptococcus has doubled since 2013. Globally, new or improved antifungals are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions.Read full original descriptionShow less
Platform Trial For Cryptococcal Meningitis
Cryptococcal meningitis is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in low and middle income countries where the ongoing HIV/AIDS pandemic increases the risk of cryptococcosis among persons living with HIV infection. The combination of amphotericin and flucytosine (5-FC) has been the mainstay of therapy for the initial management of cryptococcal meningitis for 4 decades. Indeed, the effective delivery of these first line therapy in Africa can lower mortality to 25%. However, several challenges exist. First, even while 5-FC is included on the WHO list of essential medicines, the availability of 5-FC worldwide is limited. Second, liposomal amphotericin (Ambisome ®) is currently available from a single source supplier, creating risk. Third, current therapies have substantial toxicity. Lastly, with widespread agricultural fungicide use of azoles, the median fluconazole minimum inhibitory concentration (MIC50 ) for Cryptococcus has doubled since 2013. Globally, new or improved antifungals are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions.
As multiple new antifungal medicines are on the horizon, this platform trial utilizes a master protocol to investigate, multiple antifungal regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.
Inclusion: CSF cryptococcal antigen (CrAg) positive meningitis; Living with HIV; Ability and willingness to provide informed consent; Willing to receive protocol-specified lumbar punctures; Age >= 18 years; Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use reliable forms of contraception (duration will be indicated in each Trial Appendix).
Exclusion: Received 3 or more doses of antifungal therapy for meningitis within last 30 days; Receiving chemotherapy or corticosteroids; Receiving hemodialysis or known liver cirrhosis; Previous administration of investigational study drug; Trial Appendix study-drug specific eligibility criteria; Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS); Any condition for which participation would not be in the best interest of the participant or that could limit protocol specified assessments; Inability to take enteral (oral or nasogastric) medicine; Cannot or unlikely to attend regular clinic visits; Pregnancy or breastfeeding.