High-Dose Fluconazole for the Treatment of Cryptococcal Meningitis in HIV-Infected Individuals
Summary
Cryptococcal meningitis (CM) is an infection of the membranes covering the brain and spinal cord, caused by the fungus Cryptococcus neoformans. CM most often affects people with compromised immune systems, like those with advanced HIV infection. This study explored the safety, tolerability, and therapeutic effect of a new treatment regimen with high-dose fluconazole for management of CM in HIV-infected patients.
Timeline
- Start
- 2010-04-16
- Primary completion
- 2017-01-12
- Completion
- 2017-01-12
Outcome
Missed primary endpoint
paper had similar times to achieve CSF sterilization, but took significantly longer than AMB. PMID 36780493 ↗
paper mortality was numerically lower in the AMB compared to 1600mg and 2000mg FCZ PMID 36780493 ↗
registry analysis (superiority test); Fluconazole 1200mg vs Ampho B; p = 0.0894; Log Rank NCT00885703 ↗
registry analysis (superiority test); Fluconazole 1600mg vs Ampho B; p = 0.4828; Log Rank NCT00885703 ↗
registry analysis (superiority test); Fluconazole 2000mg vs Ampho B; p = 0.1766; Log Rank NCT00885703 ↗
Publications
- Background Bicanic T, Meintjes G, Rebe K, Williams A, Loyse A, Wood R, Hayes M, Jaffar S, Harrison T. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):130-4. doi: 10.1097/QAI.0b013e3181a56f2e.
- Background Pappalardo MC, Szeszs MW, Martins MA, Baceti LB, Bonfietti LX, Purisco SU, Baez AA, Melhem MS. Susceptibility of clinical isolates of Cryptococcus neoformans to amphotericin B using time-kill methodology. Diagn Microbiol Infect Dis. 2009 Jun;64(2):146-51. doi: 10.1016/j.diagmicrobio.2009.02.007. Epub 2009 Apr 2.
- Background Seddon J, Mangeya N, Miller RF, Corbett EL, Ferrand RA. Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution. Int J STD AIDS. 2009 Apr;20(4):274-5. doi: 10.1258/ijsa.2008.008312.
- Lalloo UG, Komarow L, Aberg JA, Clifford DB, Hogg E, McKhann A, Bukuru A, Lagat D, Pillay S, Mave V, Supparatpinyo K, Samaneka W, Langat D, Ticona E, Badal-Faesen S, Larsen RA; ACTG A5225 Team. Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group. PLoS One. 2023 Feb 13;18(2):e0281580. doi: 10.1371/journal.pone.0281580. eCollection 2023.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Amphotericin B | Unknown | 0.7 mg/kg | Intravenous |
| Comparator | Amphotericin B | Unknown | 1 mg/kg | Intravenous |
| Subject | Fluconazole | Small molecule | 1200 mg | Oral |
| Subject | Fluconazole | Small molecule | 1600 mg | Oral |
| Subject | Fluconazole | Small molecule | 2000 mg | Oral |