High dose fluconazole with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitiscryptococcal meningitis

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN02725351
• Date of registration: 20/03/2008
• Prospective Registration: No
• Primary sponsor: St George's University of London (UK)
• Public title: High dose fluconazole with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitiscryptococcal meningitis
• Scientific title: A randomised controlled clinical trial to evaluate high dose fluconazole with or without flucytosine in the treatment of human immunodeficiency virus (HIV)-associated cryptococcal meningitis
• Date of first enrolment: 18/02/2008
• Target sample size: 80
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN02725351
• Study type: Interventional
• Study design: Randomised open-labelled controlled trial (Treatment)

Countries of recruitment

Malawi

Contacts

• Name: Thomas Harrison

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients greater than 18 years, either sex
2. A first episode of cryptococcal meningitis
Exclusion criteria: 1. Alanine aminotransferase (ALT) greater than five times the upper limit of normal
2. Pregnancy or lactation
3. Previous serious reaction to study drugs
4. Taking systemic anti-fungals
5. Polymorphonuclear leukocytes (PMNs) less than 500 x 10^6/L
6. Platelets less than 50,000 x 10^6/L
7. Concomitant medication that is contraindicated with any study drugs
8. Already on antiretroviral therapy (ART)

STEP 2 additional criteria:
9. Initial creatinine greater than 2.5 mg/dl

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Cryptococcal meningitis/ HIV
Infections and Infestations
Human immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases

Intervention(s)

Step 1:
1. Fluconazole 1,200 mg/d for two weeks
2. Fluconazole 1,200 mg/d plus flucytosine 100 mg/kg/d for two weeks
After two weeks all patients receive fluconazole 800 mg/d.

Step 2:
1. Amphotericin B 1 mg/kg daily for 7 days plus fluconazole 1200 mg/d (started concurrently) for 2 weeks
2. Amphotericin B 1 mg/kg daily for 7 days, plus fluconazole 1200 mg/d, plus flycytosine 100 mg/kg/day (started concurrently) for 2 weeks
After two weeks all patients receive fluconazole 800 mg/d.

Primary Outcome(s)

Early fungicidal activity (rate of clearance of infection) of alternative regimens over the first two weeks of therapy.

Secondary Outcome(s)

1. Clinical and laboratory side effects
2. Mortality at 2 and 10 weeks

Secondary ID(s)

MRC (UK) ref: 76201; 1.0

Source(s) of Monetary Support

Medical Research Council (UK) (grant ID: 76201)