Comparing antifungal treatment options for cryptococcal meningitis in people with HIV.
Platform Trial For Cryptococcal Meningitis
This will test several antifungal medicines to see which works best for adults with HIV who have cryptococcal meningitis.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 2000 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Minnesota Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 2 sites (Kampala and 1 other locations) |
| Trial ID | NCT06666322 on ClinicalTrials.gov |
What this trial studies
This Phase 2/3 platform trial randomly assigns adults living with HIV and CSF cryptococcal antigen–positive meningitis to one of several antifungal regimens, including standard of care and investigational agents such as oteseconazole and Sfu-AM2-19. The platform design allows treatment arms to be added or dropped based on safety and early efficacy signals, with participants receiving protocol-specified lumbar punctures and close clinical follow-up. Key outcomes include mortality, drug-related toxicity, and the feasibility of delivering therapies in low-resource settings. The goal is to find regimens that are safer, more accessible, or more effective than current amphotericin-based approaches.
Who should consider this trial
Good fit: Adults (≥18) living with HIV who have CSF cryptococcal antigen–positive meningitis, can consent, agree to lumbar punctures and clinic visits, and are not pregnant or breastfeeding.
Not a fit: People who have already received three or more doses of antifungal therapy in the prior 30 days, cannot take enteral medicines, are pregnant or breastfeeding, are on dialysis, have cirrhosis, are receiving chemotherapy or corticosteroids, have suspected paradoxical IRIS, or previously received the investigational drug are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, the trial could identify safer, more effective, or more accessible antifungal regimens that reduce deaths from cryptococcal meningitis in people with HIV.
How similar studies have performed: Combination amphotericin and flucytosine has previously reduced mortality from cryptococcal meningitis, but testing newer antifungal agents and a multi-arm platform approach in this setting is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * Received 3 or more doses of antifungal therapy for meningitis within last 30 days * Inability to take enteral (oral or nasogastric) medicine * Cannot or unlikely to attend regular clinic visits * Receiving chemotherapy or corticosteroids * Receiving hemodialysis or known liver cirrhosis * Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS) * Pregnancy or breastfeeding * Previous administration of investigational study drug * Any condition for which participation would not be in the best interest of the participant or that could limit protocol specified assessments * Trial Appendix study-drug specific eligibility criteria
Where this trial is running
Kampala and 1 other locations
- Infectious Diseases Institute — Kampala, Uganda (Recruiting)
- Mbarara University of Science and Technology — Mbarara, Uganda (Recruiting)
Study contacts
- Principal investigator: David R Boulware, MD, MPH — University of Minnesota
- Study coordinator: David Boulware, MD, MPH
- Email: coat.trial@gmail.com
- Phone: 612-624-9996
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.