A trial to understand how a new formulation of flucytosine works in the body among people with early cryptococcal disease
- Conditions
- Individuals with advanced HIV disease, without symptoms of meningitis, who are blood-cryptococcal antigen-positive (CrAg) and cerebrospinal fluid (CSF) CrAg-negative or who decline lumbar puncture (LP)Infections and Infestations
- Registration Number
- ISRCTN18180872
- Lead Sponsor
- Wits Health Consortium (Pty) Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 36
1. Consecutive patients aged >=18 years
2. HIV-seropositive
3. CD4 count of <200 cells/µl
4. Serum/plasma CrAg test positive within the last 21 days
5. CSF CrAg test negative or LP not done (declined)
6. Willing to participate in the study
1. Prior episode of CM or cryptococcal antigenaemia
2. Pregnancy (confirmed by urine or serum pregnancy test) or breastfeeding
3. Women of childbearing potential who do not agree to use contraception during the study period.
4. Male participants (or their female partners of childbearing potential) who do not agree to use effective contraception during the study period.
5. Already taking high-dose fluconazole treatment (800-1200 mg/day) for =10 days
6. Known dihydropyridine dehydrogenase (DPD) deficiency
7. Previous serious reaction to flucytosine or fluconazole
8. Contraindicated concomitant medications including: cisapride and the class of antihistamines including terfenadine
9. HIV-seronegative
10. Clinical symptoms/ signs of symptomatic meningitis at any time since CrAg screening, i.e. a progressively severe headache OR a headache and marked nuchal rigidity OR a headache and vomiting OR seizures OR a Glasgow Coma Scale (GCS) score of <15
11. CSF positive for CM (i.e. positive microscopy with India Ink, culture, or CrAg test) at any time between the CrAg test and screening for eligibility
12. Jaundice
13. Participants <40 kg or BMI<16 (with severe signs of malnutrition)
14. History of radiotherapy
15. Additional serious or life-threatening disease or HIV-related complications or co-morbidities (notably, diseases affecting gastrointestinal tract and participants likely to die within 14 days from conditions other than cryptococcal disease) based on the opinion of the investigator
16. Absolute neutrophil count of <500 x 106/L on baseline blood testing
17. Platelets <50,000x106/L on baseline blood testing
18. Creatinine clearance; eGFR < 60 ml/min on baseline blood testing (calculation method Cockroft/Gault)
19. Hepatic impairment (transaminases >3x upper limit of normal) on baseline blood testing
20. Participants should be excluded in case of any severe medical or psychiatric condition that may increase the risk associated with trial participation or may interfere with the interpretation of trial results.
21. Late exclusion criteria: Microbiological evidence of CM on CSF if full CSF results are not available at randomisation (e.g. screening CSF CrAg negative but culture on the same sample later returns positive for CM)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method