Cryptococcal meningitis in HIV patients Infections and Infestations Cerebral cryptococcosis
Conditions
Interventions
Sponsors
Eligibility
Inclusion criteria
Inclusion criteria: 1. Consecutive patients aged >18 years with a first episode of cryptococcal meningitis (CSF India ink or CrAg test) 2. Known to be HIV positive or willing to undertake an HIV test 3. Willing to participate in the study or, if unable to consent, has a next of kin who agrees to the patient participating in the study
Exclusion criteria
Exclusion criteria: 1. Pregnancy (confirmed by urinary or serum pregnancy test) or lactation 2. Previous serious reaction to study drugs 3. Already taking antifungal treatment at cryptococcal meningitis treatment doses (amphotericin B =0.7 mg/kg or fluconazole =800 mg/day) for >48 hours 4. Concomitant medication that is contraindicated with study drugs 5. HIV negative
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All-cause mortality within the first 10 weeks after randomisation (non-inferiority) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Early fungicidal activity, derived from serial lumbar punctures on days 1, 7 and 14 2. Clinical and laboratory-defined grade III/IV adverse events; median % change from baseline in laboratory defined parameters as and when AEs occur 3. Pharmacokinetic parameters and pharmacokinetic/pharmcodynamic associations of single high-dose L-AmB at 3, 6, 8 and 24 hours post L-AmB dose 4. Health service costs within the first 10 weeks 5. All-cause mortality within the first 2 and 4 weeks 6. All-cause mortality within the first 10 weeks (superiority) 7. Rates of cryptococcal relapse/immune reconstitution inflammatory syndrome within the first 10 weeks 8. Disability, measured using a simple two-question assessment and modified Rankin Score at 10 weeks | — |
Countries
Botswana, Malawi, South Africa, Uganda, Zimbabwe