Consent and randomisation
|
Eligibility criteria
|
X
|
X
| | | | | | | | | | | | | | | | | | |
PIS and signed consent
|
X
|
X
| | | | | | | | | | | | | | | | | | |
Randomisation
|
X
|
X
| | | | | | | | | | | | | | | | | | |
Treatment
|
Intervention: Ambisome 10 mg/kg
| |
X
| | | | | | | | | | | | | | | | | | |
Intervention: Fluconazole 1200 mg/day
| |
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | |
Intervention: Flucytosine 100 mg/kg/day
| |
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | |
Control: Amphotericin B deoxycholate 1 mg/kg
| |
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | | | | | | | | |
Control: Flucytosine 100 mg/kg/day
| |
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | | | | | | | | |
Control: Fluconazole 1200 mg/day
| | | | | | | | |
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | |
All participants: Fluconazole 800 mg/day
| | | | | | | | | | | | | | |
X
|
X
|
X
|
X
|
X
| |
All participants: 200 mg/day
| | | | | | | | | | | | | | | | | | |
X
|
X
|
Clinical, safety and compliance assessment
|
Inpatient clinical review
| |
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| | | | | |
Outpatient follow-up
| | | | | | | | | | | | | | | |
X
|
X
|
X
|
X
| |
Week 16 telephone
| | | | | | | | | | | | | | | | | | | |
X
|
Clinical labs
|
HIV testing
| |
X
| | | | | | | | | | | | | | | | | | |
Pregnancy test (urine/serum)a
| |
X
| | | | | | | | | | | | | | | | | | |
Full blood count
| |
X
| | | | | |
X
| | | | | | |
X
|
X
| | | | |
CD4 count
| |
X
| | | | | | | | | | | | | | | | | | |
ALT
| |
X
| | | | | |
X
| | | | | | |
X
|
X
| | | | |
Urea, creatinine and electrolytes
| |
X
| |
X
| |
X
| |
X
| | |
X
| |
X
| |
X
|
X
| | | | |
Drug levels
| |
X
| | | | | |
X
| | | | | | | | | | | | |
Quantitative PCR sub-study
| |
X
| |
X
| | | |
X
| | | | | | |
X
| | | | | |
Semi-quantitative cryptococcal antigen
| |
X
| | | | | | | | | | | | | | | | | | |
CSF
|
Opening pressure
| |
X
| | | | | |
X
| | | | | | |
X
| | | | | |
Cell count and differentialb
| |
X
| | | | | | | | | | | | | | | | | | |
Protein, glucoseb
| |
X
| | | | | | | | | | | | | | | | | | |
Routine cultureb
| |
X
| | | | | | | | | | | | | | | | | | |
India ink examinationb,c
| |
X
| | | | | | | | | | | | | | | | | | |
Cryptococcal antigenb,c
| |
X
| | | | | | | | | | | | | | | | | | |
Quantitative fungal culture
| |
X
| | | | | |
X
| | | | | | |
X
| | | | | |
CSF drug levels
| |
X
| | | | | |
X
| | | | | | |
X
| | | | | |
Immune parameters
| |
X
| | | | | |
X
| | | | | | |
X
| | | | | |
Semi-quantitative cryptococcal antigen
| |
X
| | | | | | | | | | | | | | | | | | |