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

Phase 3

Completed

• Conditions: Cryptococcal meningitis in HIV patients; Infections and Infestations; Cerebral cryptococcosis

• Registration Number: ISRCTN72509687
• Lead Sponsor: ondon School of Hygiene and Tropical Medicine

Brief Summary

2018 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/30470259 protocol 2019 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/30940760 economic evaluation protocol (added 04/04/2019) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35320642/ (added 24/03/2022) 2022 Other publications in https://pubmed.ncbi.nlm.nih.gov/36322466/ Analysis of HIV drug resistance mutations (added 03/11/2022) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36400090/ Cost-effectiveness (added 21/11/2022) 2024 Other publications in https://pubmed.ncbi.nlm.nih.gov/39189739/ sub-study (added 02/09/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-13
• Study Completion: 2021-06-30
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 844

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

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 =0.7mg/kg or fluconazole =800mg/day) for >48 hours
4. Concomitant medication that is contraindicated with study drugs
5. HIV negative

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
All-cause mortality within the first 10 weeks after randomisation (non-inferiority)

Secondary Outcome Measures

Name	Time	Method
1. Early fungicidal activity, derived from serial lumbar punctures on days 1, 7 and 14<br>2. Clinical and laboratory-defined grade III/IV adverse events; median % change from baseline in laboratory defined parameters as and when AEs occur <br>3. Pharmacokinetic parameters and pharmacokinetic/pharmcodynamic associations of single high-dose L-AmB at 3, 6, 8 and 24 hours post L-AmB dose<br>4. Health service costs within the first 10 weeks<br>5. All-cause mortality within the first 2 and 4 weeks<br>6. All-cause mortality within the first 10 weeks (superiority)<br>7. Rates of cryptococcal relapse/immune reconstitution inflammatory syndrome within the first 10 weeks<br>8. Disability, measured using a simple two-question assessment and modified Rankin Score at 10 weeks