Jarvis, Joseph N; Lawrence, David S; Meya, David B; Kagimu, Enock; Kasibante, John; Mpoza, Edward; Rutakingirwa, Morris K; Ssebambulidde, Kenneth; Tugume, Lillian; Rhein, Joshua; +33 more... Boulware, David R; Mwandumba, Henry C; Moyo, Melanie; Mzinganjira, Henry; Kanyama, Cecilia; Hosseinipour, Mina C; Chawinga, Chimwemwe; Meintjes, Graeme; Schutz, Charlotte; Comins, Kyla; Singh, Achita; Muzoora, Conrad; Jjunju, Samuel; Nuwagira, Edwin; Mosepele, Mosepele; Leeme, Tshepo; Siamisang, Keatlaretse; Ndhlovu, Chiratidzo E; Hlupeni, Admire; Mutata, Constantine; van Widenfelt, Erik; Chen, Tao; Wang, Duolao; Hope, William; Boyer-Chammard, Timothée; Loyse, Angela; Molloy, Síle F; Youssouf, Nabila; Lortholary, Olivier; Lalloo, David G; Jaffar, Shabbar; Harrison, Thomas S; Ambition Study Group; (2022) Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. New England Journal of Medicine, 386 (12). pp. 1109-1120. ISSN 0028-4793 DOI: https://doi.org/10.1056/NEJMoa2111904
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Abstract
BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
PubMed ID | 35320642 |
Elements ID | 175495 |
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