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High dose AMBISOME on a fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa

High dose AMBISOME on a fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: a Phase 3 randomised controlled non-Inferiority trial

Status
Active, not recruiting
Phases
Phase 3
Study type
Interventional
Source
ISRCTN
Registry ID
ISRCTN72509687
Enrollment
850
Registered
2017-07-13
Start date
2017-09-01
Completion date
Unknown
Last updated
2025-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cryptococcal meningitis in HIV patients Infections and Infestations Cerebral cryptococcosis

Interventions

Current interventions as of 01/08/2018: 850 patients will be enrolled and randomised 1:1 into two arms: 1. L-AmB 10 mg/kg day 1 (single dose) 2. Amphotericin-B 1mg/kg/d for 7 days (standard dose “cont

Sponsors

London School of Hygiene and Tropical Medicine
Lead Sponsor

Eligibility

Sex/Gender
All

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

MeasureTime frame
All-cause mortality within the first 10 weeks after randomisation (non-inferiority)

Secondary

MeasureTime 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

Contacts

Public ContactJoe Jarvis

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Mar 4, 2026