Trial reportAIDS (London, England)2012
A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis.
Trial report in AIDS (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.The Lancet. Infectious diseases · 2024Guideline
- Equity in clinical trials for HIV-associated cryptococcal meningitis: A systematic review of global representation and inclusion of patients and researchers.PLoS neglected tropical diseases · 2021Pooled it
- Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management.Medical mycology · 2020Pooled it
- Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.Journal of the International AIDS Society · 2020Pooled it
- Treatment for HIV-associated cryptococcal meningitis.The Cochrane database of systematic reviews · 2018Pooled it
- Pooled it
- Cryptococcal Meningitis: Comparison of Short- (≤ 1 Week) Versus Longer-duration (> 1 Week) Liposomal Amphotericin B Induction Therapy and Factors Associated With Clinical Outcomes in HIV and Non-HIV Patients.Open forum infectious diseases · 2026Trial
- Trial
- Bioavailability of a novel sustained-release pellet formulation of 5-flucytosine in healthy-fed participants for use in patients with cryptococcal meningitis.Clinical and translational science · 2024Trial
- How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis to High-Income Settings?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Trial
- Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.The New England journal of medicine · 2022Trial
- Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.PLoS neglected tropical diseases · 2020Trial
- Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Trial
- Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis.Antimicrobial agents and chemotherapy · 2015Trial
- Trial
- HIV-Associated Cryptococcal Meningitis: A Call for Action for New Treatment Options.Therapeutics · 2026Article
- Assessing Statistical Methods for Estimating the Cerebrospinal Fluid Early Fungicidal Activity as an Endpoint for Cryptococcal Meningitis Clinical Trials: A Systematic Review and Simulation Study.Open forum infectious diseases · 2026Article
- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundCryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500 000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB).
methodsIn step 1, previously reported, patients were randomized to receive FLU 1200 mg per day with or without 5-FC 100 mg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1 mg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality.
resultsForty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU: -0.50 ± 0.15 log CFU/day vs. -0.38 ± 0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28 ± 0.17) or FLU alone (-0.11 ± 0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, P = 0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, P = 0.1).
conclusionAddition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.
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