Trial reportTrials2015
AMBITION-cm: intermittent high dose AmBisome on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: study protocol for a randomized controlled trial.
Trial report in Trials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 25 citations in OpenAlex.
- Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial.Thorax · 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
- Article
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches.Life (Basel, Switzerland) · 2021Review
- Genome-Wide Association Study Identifies Novel Colony Stimulating Factor 1 Locus Conferring Susceptibility to Cryptococcosis in Human Immunodeficiency Virus-Infected South Africans.Open forum infectious diseases · 2020Article
- Antifungal Agents in Agriculture: Friends and Foes of Public Health.Biomolecules · 2019Review
- Adaptive designs in clinical trials in critically ill patients: principles, advantages and pitfalls.Intensive care medicine · 2019Article
- Diagnostic and therapeutic strategies in cryptococcosis: impact on outcome.Memorias do Instituto Oswaldo Cruz · 2018Review
- Retrospective Cohort Analysis of Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies.Antimicrobial agents and chemotherapy · 2017Article
- High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis.Scientific reports · 2017Article
- Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings.Expert review of anti-infective therapy · 2017Review
- Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.Nature reviews. Neurology · 2017Review
- Cryptococcal Disease in HIV-Infected Children.Current infectious disease reports · 2016Review
- Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis.Open forum infectious diseases · 2015Article
- HIV-Associated Cryptococcal Meningitis: Bridging the Gap Between Developed and Resource-Limited Settings.Current clinical microbiology reportsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 14 institutions in 9 countries.
Funding
Abstract
backgroundCryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM. METHODOLOGY/
designThis is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥ 18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400-800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat.
trial registrationISRCTN10248064. Date of Registration: 22 January 2014.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.