Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal

Status Recruiting

Clinical Trial Summary

Cryptococcal meningitis (CM) 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 Africa where the ongoing HIV/AIDS pandemic leads to higher prevalence of cryptococcosis. Combination of amphotericin and flucytosine (5-FC) is the mainstay of therapy for the initial management of CM. Indeed, it has even been shown that effective delivery of these therapies in Africa can lower mortality rates by 90%. This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing. Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed. Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received. Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days. The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mg/day. All participants will receive fluconazole 1200mg/day during consolidation therapy from day 1 to 14 then 800mg/day from day 15 to 10 weeks, and 200mg/day after 10 weeks. All participants will receive lumbar punctures at diagnosis, day 3, day 5-7, day 10-14, and additionally as required for control of intracranial pressure and documentation of CSF sterilization. Controls from Ambition will be matched for the same LP windows. Therapeutic LPs conducted during the first week have a ~70% relative survival benefit.

Clinical Trial Description

n/a

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT06414512
Study type	Interventional
Source	University of Minnesota
Contact	David Boulware
Email	coat.trial@gmail.com
Status	Recruiting
Phase	Phase 2
Start date	April 9, 2024
Completion date	September 1, 2024

View Details

See also
Status	Clinical Trial	Phase
Completed	`NCT01589289` - Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases in Neurological Disorders in DRC	Phase 3
Completed	`NCT00976040` - Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis	Phase 4
Completed	`NCT04031833` - Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial (EnACT)	Phase 1/Phase 2
Completed	`NCT00830856` - Early Versus Delayed Antiretroviral Therapy (ART) in the Treatment of Cryptococcal Meningitis in Africa	N/A
Completed	`NCT04532463` - Clinical Effectiveness and Safety of Amphotericin B With Flucytosine-Fluconazole Therapy for Cryptococcal Meningitis
Completed	`NCT02098525` - Clinical Outcomes of Cryptococcal Meningitis Among HIV-infected Patients in the Era of Antiretroviral Therapy	N/A
Completed	`NCT01075152` - Cryptococcal Optimal ART Timing Trial	Phase 4
Active, not recruiting	`NCT01715922` - Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa	Phase 2/Phase 3
Completed	`NCT00145249` - Amphotericin Alone or in Combination With Fluconazole for AIDS-Associated Meningitis	Phase 2
Completed	`NCT01802385` - Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis	Phase 3
Terminated	`NCT00324025` - Efficacy and Safety of Mycograb as Adjunctive Therapy for Cryptococcal Meningitis in Patients With AIDS	Phase 2
Completed	`NCT02955862` - Vietnam Cryptococcal Retention in Care Study (CRICS) Federal Financial Report	Phase 1
Recruiting	`NCT03945448` - Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia	Phase 2/Phase 3
Active, not recruiting	`NCT02624453` - Pre-Antiretroviral Therapy (ART) Cryptococcal Antigen Screening in AIDS	N/A
Recruiting	`NCT00867269` - Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Completed	`NCT01535469` - Operational Research for Cryptococcal Antigen Screening	Phase 4
Active, not recruiting	`NCT04072640` - Three Induction Treatments on Cryptococcal Meningitis	Early Phase 1
Not yet recruiting	`NCT05541107` - Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3	Phase 3
Not yet recruiting	`NCT02686853` - Efficacy of Intrathecal Administration of Liposomal Amphotericin B in Cryptococcal Meningitis	Phase 4
Not yet recruiting	`NCT04140461` - AmB Dose for Cryptococcal Meningitis	Phase 3

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal Meningitis

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms