Cryptococcal Meningitis
Conditions
Brief summary
This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda. Patients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg/kg) in addition to standard of care fluconazole therapy. How the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.
Interventions
DRUGSingle dose liposomal Amphotericin and Fluconazole
Intravenous Single dose of 10mg/kg of Ambisome and fluconazole as per WHO guidelines for six months.
DRUGFluconazole
Fluconazole 800mg for 2 weeks,400mg for 8 weeks and 200mg up to six months
Sponsors
Makerere University
University of Minnesota
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * Age \> or equal to15 years * Ability and willingness to give informed consent. * Plasma/Serum cryptococcal antigen (CRAG)+ with a titer 1:160 or greater
Exclusion criteria
* Cannot or unlikely to attend regular clinic visits * History of cryptococcal infection * Symptomatic meningitis (confirmed by CSF CRAG+) * \>14 days of fluconazole therapy * Pregnancy (confirmed by urinary or serum pregnancy test) * Current breastfeeding * Known allergy to amphotericin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients that develop meningitis in the AMBISOME arm compared to the fluconazole arm. | 24 weeks | Comparison will be made between those randomized to single dose liposomal amphotericin + standard of care (fluconazole) vs. standard of care (fluconazole) alone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of grade 3 to 5 clinical adverse events or serious adverse events | within two weeks of enrollment | Symptoms causing inability to perform social and functional activities and potentially life threatening symptoms requiring intervention or hospitalization. |
| Number of grade 3 to 5 laboratory adverse events by NIAID DAIDS toxicity scale | within two weeks of enrollment | Abnormal laboratory findings that meet the DAIDS categorization of grade 3 and 4. |
| Cost-effectiveness of single dose liposomal amphotericin + fluconazole compared to fluconazole preemptive therapy alone, and compared to no preemptive therapy. | 24 weeks | what will be the added cost required to treat patients with AMBISOME when assessed in light of the outcomes. |
| Number of patients that will survive in the 24-week period. | 24 weeks | How many patients will be alive at 24 weeks when the two arms are compared. |
Countries
Uganda
Contacts
CONTACTDAVID MEYA, PhD
CONTACTELIZABETH NALINTYA, MPH
Outcome results
None listed