Antifungal Therapies for Cryptococcal Meningitis
(PLATFORM-CM Trial)
Trial Summary
What is the purpose of this trial?
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 regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.
Research Team
David R Boulware, MD, MPH
Principal Investigator
University of Minnesota
David B Meya, MBChB, MMed, PhD
Principal Investigator
Uganda
Eligibility Criteria
This trial is for individuals with cryptococcal meningitis, often linked to HIV. Participants must consent to the study procedures, including lumbar punctures, and women able to become pregnant must use contraception. Those with CSF cryptococcal antigen positive meningitis are eligible.Inclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive either standard of care or one of the experimental antifungal therapies
Follow-up
Participants are monitored for safety and effectiveness after treatment, including survival and adverse events
Treatment Details
Interventions
- Antifungal therapy 3
- Antifungal therapy 4
- Oteseconazole
- Sfu-AM2-19 Injection
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Minnesota
Lead Sponsor